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Introduction: With the application of high-resolution 3D 7 Tesla Magnetic Resonance Spectroscopy Imaging (MRSI) in high-grade gliomas, we previously identified intratumoral metabolic heterogeneities. In this study, we evaluated the potential of 3D 7 T-MRSI for the preoperative noninvasive classification of glioma grade and isocitrate dehydrogenase (IDH) status. We demonstrated that IDH mutation and glioma grade are detectable by ultra-high field (UHF) MRI. This technique might potentially optimize the perioperative management of glioma patients., Methods: We prospectively included 36 patients with WHO 2021 grade 2-4 gliomas (20 IDH mutated, 16 IDH wildtype). Our 7 T 3D MRSI sequence provided high-resolution metabolic maps (e.g., choline, creatine, glutamine, and glycine) of these patients' brains. We employed multivariate random forest and support vector machine models to voxels within a tumor segmentation, for classification of glioma grade and IDH mutation status., Results: Random forest analysis yielded an area under the curve (AUC) of 0.86 for multivariate IDH classification based on metabolic ratios. We distinguished high- and low-grade tumors by total choline (tCho) / total N-acetyl-aspartate (tNAA) ratio difference, yielding an AUC of 0.99. Tumor categorization based on other measured metabolic ratios provided comparable accuracy., Conclusions: We successfully classified IDH mutation status and high- versus low-grade gliomas preoperatively based on 7 T MRSI and clinical tumor segmentation. With this approach, we demonstrated imaging based tumor marker predictions at least as accurate as comparable studies, highlighting the potential application of MRSI for pre-operative tumor classifications., (© 2024. The Author(s).)

Purpose: Recently, a 3D-concentric ring trajectory (CRT)-based free induction decay (FID)-MRSI sequence was introduced for fast high-resolution metabolic imaging at 7 T. This technique provides metabolic ratio maps of almost the entire brain within clinically feasible scan times, but its robustness has not yet been thoroughly investigated. Therefore, we have assessed quantitative concentration estimates and their variability in healthy volunteers using this approach., Methods: We acquired whole-brain 3D-CRT-FID-MRSI at 7 T in 15 min with 3.4 mm nominal isometric resolution in 24 volunteers (12 male, 12 female, mean age 27 ± 6 years). Concentration estimate maps were calculated for 15 metabolites using internal water referencing and evaluated in 55 different regions of interest (ROIs) in the brain. Data quality, mean metabolite concentrations, and their inter-subject coefficients of variation (CVs) were compared for all ROIs., Results: Of 24 datasets, one was excluded due to motion artifacts. The concentrations of total choline, total creatine, glutamate, myo-inositol, and N-acetylaspartate in 44 regions were estimated within quality thresholds. Inter-subject CVs (mean over 44 ROIs/minimum/maximum) were 9%/5%/19% for total choline, 10%/6%/20% for total creatine, 11%/7%/24% for glutamate, 10%/6%/19% for myo-inositol, and 9%/6%/19% for N-acetylaspartate., Discussion: We defined the performance of 3D-CRT-based FID-MRSI for metabolite concentration estimate mapping, showing which metabolites could be robustly quantified in which ROIs with which inter-subject CVs expected. However, the basal brain regions and lesser-signal metabolites in particular remain as a challenge due susceptibility effects from the proximity to nasal and auditory cavities. Further improvement in quantification and the mitigation of B 0 /B 1 -field inhomogeneities will be necessary to achieve reliable whole-brain coverage., (© 2021 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

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 mm nominal voxel size acquired in ~3 minutes to an 80 × 80 × 47 matrix with 2.7 × 2.7 × 2.7 mm 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.

Purpose: A properly characterized macromolecular (MM) contribution is essential for accurate metabolite quantification in FID-MRSI. MM information can be included into the fitting model as a single component or parameterized and included over several individual MM resonances, which adds flexibility when pathologic changes are present but is prone to potential overfitting. This study investigates the effects of different MM models on MRSI reproducibility., Methods: Clinically feasible, high-resolution FID-MRSI data were collected in ~5 min at 7 Tesla from 10 healthy volunteers and quantified via LCModel (version 6.3) with 3 basis sets, each with a different approach for how the MM signal was handled: averaged measured whole spectrum (full MM), 9 parameterized components (param MM) with soft constraints to avoid overparameterization, or without any MM information included in the fitting prior knowledge. The test-retest reproducibility of MRSI scans was assessed voxel-wise using metabolite coefficients of variation and intraclass correlation coefficients and compared between the basis sets. Correlations of concentration estimates were investigated for the param MM fitting model., Results: The full MM model provided the most reproducible quantification of total NAA, total Cho, myo-inositol, and glutamate + glutamine ratios to total Cr (coefficients of variations ≤ 8%, intraclass correlation coefficients ≥ 0.76). Using the param MM model resulted in slightly lower reproducibility (up to +3% higher coefficients of variations, up to -0.1 decreased intraclass correlation coefficients). The quantification of the parameterized macromolecules did not affect quantification of the overlapping metabolites., Conclusion: Clinically feasible FID-MRSI with an experimentally acquired MM spectrum included in prior knowledge provides highly reproducible quantification for the most common neurometabolites in healthy volunteers. Parameterization of the MM spectrum may be preferred as a compromise between quantification accuracy and reproducibility when the MM content is expected to be pathologically altered., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: To demonstrate the feasibility of 7 T magnetic resonance spectroscopic imaging (MRSI), combined with patch-based super-resolution (PBSR) reconstruction, for high-resolution multi-metabolite mapping of gliomas., Materials and Methods: Ten patients with WHO grade II, III and IV gliomas (6/4, male/female; 45 ± 9 years old) were prospectively measured between 2014 and 2018 on a 7 T whole-body MR imager after routine 3 T magnetic resonance imaging (MRI) and positron emission tomography (PET). Free induction decay MRSI with a 64 × 64-matrix and a nominal voxel size of 3.4 × 3.4 × 8 mm³ was acquired in six minutes, along with standard T1/T2-weighted MRI. Metabolic maps were obtained via spectral LCmodel processing and reconstructed to 0.9 × 0.9 × 8 mm³ resolutions via PBSR., Results: Metabolite maps obtained from combined 7 T MRSI and PBSR resolved the density of metabolic activity in the gliomas in unprecedented detail. Particularly in the more heterogeneous cases (e.g. post resection), metabolite maps enabled the identification of complex metabolic activities, which were in topographic agreement with PET enhancement., Conclusions: PBSR-MRSI combines the benefits of ultra-high-field MR systems, cutting-edge MRSI, and advanced postprocessing to allow millimetric resolution molecular imaging of glioma tissue beyond standard methods. An ideal example is the accurate imaging of glutamine, which is a prime target of modern therapeutic approaches, made possible due to the higher spectral resolution of 7 T systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the utility of increased spatial resolution of magnetic resonance spectroscopic imaging (MRSI) at 7 T for the detection of neurochemical changes in multiple sclerosis (MS)-related brain lesions., Materials and Methods: This prospective, institutional review board-approved study was performed in 20 relapsing-remitting MS patients (9 women/11 men; mean age ± standard deviation, 30.8 ± 7.7 years) after receiving written informed consent. Metabolic patterns in MS lesions were compared at 3 different spatial resolutions of free induction decay MRSI with implemented parallel imaging acceleration: 2.2 × 2.2 × 8 mm; 3.4 × 3.4 × 8 mm; and 6.8 × 6.8 × 8 mm voxel volumes, that is, matrix sizes of 100 × 100, 64 × 64, and 32 × 32, respectively. The quality of data was assessed by signal-to-noise ratio and Cramér-Rao lower bounds. Statistical analysis was performed using Wilcoxon signed-rank tests with correction for multiple testing., Results: Seventy-seven T2-hyperintense MS lesions were investigated (median volume, 155.7 mm; range, 10.8-747.0 mm). The mean metabolic ratios in lesions differed significantly between the 3 MRSI resolutions (ie, 100 × 100 vs 64 × 64, 100 × 100 vs 32 × 32, and 64 × 64 vs 32 × 32; P < 0.001). With the ultra-high resolution (100 × 100), we obtained 40% to 80% higher mean metabolic ratios and 100% to 150% increase in maximum metabolic ratios in the MS lesions compared with the lowest resolution (32 × 32), while maintaining good spectral quality (signal-to-noise ratio >12, Cramér-Rao lower bounds <20%) and measurement time of 6 minutes. There were 83% of MS lesions that showed increased myo-inositol/N-acetylaspartate with the 100 × 100 resolution, but only 66% were distinguishable with the 64 × 64 resolution and 35% with the 32 × 32 resolution., Conclusions: Ultra-high-resolution MRSI (~2 × 2 × 8 mm voxel volume) can detect metabolic alterations in MS, which cannot be recognized by conventional MRSI resolutions, within clinically acceptable time.

An adiabatic MEscher-GArwood (MEGA)-editing scheme, using asymmetric hyperbolic secant editing pulses, was developed and implemented in a B 1 + -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 1 + 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 3 ) 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 0 /B 1 + inhomogeneities, prolonged scan times, and motion/scanner instability artifacts. Robust and accurate 2D mapping has been shown for the neurotransmitters GABA and Glx., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Full-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 Methods: Trajectories 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 mm 2 , 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., Results: By 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., Conclusion: Density-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., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

MRSI in the brain at ≥7 T is a technique of great promise, but has been limited mainly by low B 0 /B 1 + -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 3 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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare high-resolution free induction decay magnetic resonance spectroscopic imaging (FID-MRSI) at 3 T and 7 T in the brain of healthy subjects and to showcase the clinical potential of accelerated FID-MRSI at 7 T in 2 brain tumor cases., Materials and Methods: In this institutional review board-approved study, 10 healthy volunteers (8 men/2 women; age: 31 ± 6 years) were measured at 3 T and 7 T (Trio and 7T-Magnetom; Siemens Healthcare, Germany) and 2 patients (a 38-year-old man and a 37-year-old man), 1 with an anaplastic oligoastrocytoma (grade III) and 1 with a low-grade glioma (oligodendroglioma), were measured at 7 T.Free induction decay MR spectroscopic imaging with 3.4 × 3.4 mm in-plane resolution was acquired in 30 minutes/6 minutes (nonaccelerated/accelerated) at both field strengths. In addition, single-slice or multi-slice FID-MRSI at 7 T was measured in the 2 tumor patients at 7 T within 6 minutes/13.3 minutes. Signal-to-noise ratio, Cramer-Rao lower bounds, and parallel imaging efficiency were assessed. High-resolution maps were created for 9 different brain metabolites., Results: At 7 T, 7 of 9 metabolites were reliably mapped over the whole slice but only 3 at 3 T. Parallel imaging efficiency was significantly improved at 7 T. Signal-to-noise ratios were +75%/+66% (P < 0.05) for N-acetylaspartate and +97%/+74%(P < 0.05) for glutamine + glutamate [Glx], and full-widths at half maximum were +112%/+109%(P < 0.05) higher at 7 T than at 3 T (nonaccelerated/accelerated) for N-acetylaspartate. Cramer-Rao lower bounds were more than double at 3 T (P < 0.05)., Conclusions: At 7 T, FID-MRSI allowed the assessment of an extended neurochemical profile and yielded better metabolic maps in only approximately 6 minutes at 7 T than in approximately 30 minutes at 3 T. We found several potentially therapy-relevant neurochemical alterations in brain tumors that highlighted the potential of fast clinical FID-MRSI at 7 T.

Presently, three major MR vendors provide commercial 7-T units for clinical research under ethical permission, with the number of operating 7-T systems having increased to over 50. This rapid increase indicates the growing interest in ultrahigh-field MRI because of improved clinical results with regard to morphological as well as functional and metabolic capabilities. As the signal-to-noise ratio scales linearly with the field strength (B0 ) of the scanner, the most obvious application at 7 T is to obtain higher spatial resolution in the brain, musculoskeletal system and breast. Of specific clinical interest for neuro-applications is the cerebral cortex at 7 T, for the detection of changes in cortical structure as a sign of early dementia, as well as for the visualization of cortical microinfarcts and cortical plaques in multiple sclerosis. In the imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology can be visualized with excellent resolution. The dynamic and static blood oxygenation level-dependent contrast increases linearly with the field strength, which significantly improves the pre-surgical evaluation of eloquent areas before tumor removal. Using susceptibility-weighted imaging, the plaque-vessel relationship and iron accumulation in multiple sclerosis can be visualized for the first time. Multi-nuclear clinical applications, such as sodium imaging for the evaluation of repair tissue quality after cartilage transplantation and (31) P spectroscopy for the differentiation between non-alcoholic benign liver disease and potentially progressive steatohepatitis, are only possible at ultrahigh fields. Although neuro- and musculoskeletal imaging have already demonstrated the clinical superiority of ultrahigh fields, whole-body clinical applications at 7 T are still limited, mainly because of the lack of suitable coils. The purpose of this article was therefore to review the clinical studies that have been performed thus far at 7 T, compared with 3 T, as well as those studies performed at 7 T that cannot be routinely performed at 3 T. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Purpose: To evaluate the feasibility of a one-dimensional image-selected in vivo spectroscopy (1D-ISIS) saturation transfer (ST) sequence at 7T for localized in vivo measurements of energy metabolism in different tissues in clinically reasonable examination times., Methods: The performance of a gradient offset independent adiabacity-based 1D-ISIS localization was tested on phantom and the localized ST sequence was compared with the nonlocalized version in vivo. We performed localized measurements of basal metabolism of human liver and different muscle groups of the calf. Localized ST experiments took 15-25 minutes., Results: The selectivity of the 1D-ISIS sequence was 81.63% and the outer volume suppression was 97.57%. The ST parameters acquired with the 1D-ISIS sequence and with the nonlocalized acquisition in the muscle were not statistically different. The forward rate constants for phosphocreatine (PCr)-adenosine triphosphate (ATP) and inorganic phosphate (Pi)-ATP exchange reactions were measured in the soleus (kCK  = 0.30 ± 0.06 s(-1) and kATP  = 0.11 ± 0.02 s(-1) , respectively) and in the medial gastrocnemius (kCK  = 0.27 ± 0.06 s(-1) and kATP  = 0.09 ± 0.03s(-1) , respectively) in 15 minutes per muscle group. The corresponding fluxes were FCK  = 6.26 ± 1.28 μmol/g/s, FATP  = 0.22 ± 0.05 μmol/g/s and FCK  = 6.29 ± 1.66 μmol/g/s, FATP  = 0.21 ± 0.07 μmol/g/s, for soleus and gastrocnemius, respectively. The hepatic ATP synthesis measurement was feasible in 24 minutes., Conclusion: The fast assessment of PCr-ATP and Pi-ATP exchange rates at 7T makes the 1D-ISIS ST sequence a promising tool for examining local resting-state metabolism in clinically acceptable measurement times., (© 2014 Wiley Periodicals, Inc.)

The aim of this study was to introduce a two-dimensional chemical shift imaging (2D CSI) sequence, with simultaneous acquisition of free induction decay (FID) and long TEs, for the detection and quantification of intramyocellular lipids (IMCLs) in the calf at 7 T. The feasibility of the new 2D CSI sequence, which acquires FID (acquisition delay, 1.3 ms) and an echo (long TE) in one measurement, was evaluated in phantoms and volunteers (n = 5): TR/TE*/TE = 800/1.3/156 ms; 48 × 48 matrix; field of view, 200 × 200 × 20 mm(3) ; Hamming filter; no water suppression; measurement time, 22 min 2 s. The IMCL concentration and subcutaneous lipid contamination were assessed. Spectra in the tibialis anterior (TA), gastrocnemius (GM) and soleus (SOL) muscles were analyzed. The water signal from the FID acquisition was used as an internal concentration reference. In the spectra from subcutaneous adipose tissue (SUB) and bone marrow (BM), an unsaturation index (UI) of the vinyl-H (5.3 ppm) to methyl-CH3 ratio, and a polyunsaturation index (pUI) of the diallylic-H (2.77 ppm) to -CH3 ratio, were calculated. Long-TE spectra from muscles showed a simplified spectral pattern with well-separated IMCL for several muscle groups in the same scan. The IMCL to water ratio was largest in SOL (0.66% ± 0.23%), and lower in GM (0.37% ± 0.14%) and TA (0.36% ± 0.12%). UI and pUI for SUB were 0.65 ± 0.06 and 0.18 ± 0.04, respectively, and for BM were 0.60 ± 0.16 and 0.18 ± 0.08, respectively. The new sequence, with the proposed name 'free induction decay echo spectroscopic imaging' (FIDESI), provides information on both specific lipid resonances and water signal from different tissues in the calf, with high spectral and spatial resolution, as well as minimal voxel bleeding and subcutaneous lipid contamination, in clinically acceptable measurement times., (Copyright © 2014 John Wiley & Sons, Ltd.)

Introduction: The purpose of this study was to compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a single parameter to multiparametric (MP) MRI with 2 (DCE MRI and diffusion-weighted imaging [DWI]) and 3 (DCE MRI, DWI, and 3-dimensional proton magnetic resonance spectroscopic imaging [3D H-MRSI]) parameters in breast cancer diagnosis., Materials and Methods: This prospective study was approved by the institutional review board. Written informed consent was obtained in all patients. One hundred thirteen female patients (mean age, 52 years; range, 22-86 years) with an imaging abnormality (Breast Imaging Reporting and Data System 0, 4-5) were included in this study. Multiparametric MRI of the breast at 3 T with DCE MRI, DWI, and 3D H-MRSI was performed. The likelihood of malignancy was assessed for DCE MRI and MP MRI with 2 (DCE MRI and DWI) and 3 (DCE MRI, DWI, and 3D H-MRSI) parameters separately. Histopathology was used as the standard of reference. Appropriate statistical tests were used to assess sensitivity, specificity, and diagnostic accuracy for each assessment combination., Results: There were 74 malignant and 39 benign breast lesions. Multiparametric MRI with 3 MRI parameters yielded significantly higher areas under the curve (0.936) in comparison with DCE MRI alone (0.814) (P<0.001). Multiparametric MRI with just 2 parameters at 3 T did not yield higher areas under the curve (0.808) than did DCE MRI alone (0.814). Multiparametric MRI with 3 parameters resulted in elimination of false-negative lesions and significantly reduced the false-positives ones (P=0.002)., Conclusions: Multiparametric MRI with 3 parameters increases the diagnostic accuracy of breast cancer in comparison with DCE-MRI alone and MP MRI with 2 parameters.

Phosphorus ((31) P) MRS is a powerful tool for the non-invasive investigation of human liver metabolism. Four in vivo (31) P localization approaches (single voxel image selected in vivo spectroscopy (3D-ISIS), slab selective 1D-ISIS, 2D chemical shift imaging (CSI), and 3D-CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal-to-noise ratios normalized for voxel volume and acquisition time differences, Cramer-Rao lower bounds (8.7 ± 3.3%1D-ISIS , 7.6 ± 2.5%3D-ISIS , 8.6 ± 4.2%2D-CSI , 10.3 ± 2.7%3D-CSI ), and linewidths (50 ± 24 Hz1D-ISIS , 34 ± 10 Hz3D-ISIS , 33 ± 10 Hz2D-CSI , 34 ± 11 Hz3D-CSI ). Longitudinal (T1 ) relaxation times of human liver metabolites at 7 T were assessed by 1D-ISIS inversion recovery in the same volunteers (n = 9). T1 relaxation times of hepatic (31) P metabolites at 7 T were the following: phosphorylethanolamine - 4.41 ± 1.55 s; phosphorylcholine - 3.74 ± 1.31 s; inorganic phosphate - 0.70 ± 0.33 s; glycerol 3-phosphorylethanolamine - 6.19 ± 0.91 s; glycerol 3-phosphorylcholine - 5.94 ± 0.73 s; γ-adenosine triphosphate (ATP) - 0.50 ± 0.08 s; α-ATP - 0.46 ± 0.07 s; β-ATP - 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first (31) P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR., (Copyright © 2014 John Wiley & Sons, Ltd.)

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units., (RSNA, 2014)

Phosphorous ((31)P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (kATP) and creatine kinase reaction (kCK), as well as corresponding metabolic fluxes (FATP, FCK), were estimated. A comparison of these exchange parameters, apparent T₁s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., kATP 2.7 times higher and kCK 3.4 times higher) than at 3 T (p<0.05). The values for kATP (p=0.35) and kCK (p=0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3T. The minimal time-resolution to reliably quantify both FATP and FCK at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the diagnostic accuracy of quantitative, three-dimensional (3D) magnetic resonance (MR) spectroscopic imaging at 3 T for the differentiation of benign and malignant breast lesions, on the basis of choline (Cho) signal-to-noise ratio (SNR) threshold levels, in a clinically feasible measurement time., Materials and Methods: Institutional review board approval and written informed consent were obtained from all subjects. Fifty female patients (mean age, 50 years; age range, 25-82 years) with mammographic or ultrasonographic (US) abnormalities were successfully examined in the prone position with a 3-T MR system by using a dedicated breast coil. Lesions were verified by either histopathologic examination or follow-up of at least 24 months. For 3D MR spectroscopic imaging, a point-resolved spectroscopic sequence (repetition time msec/echo time msec, 750/145; field of view, 12 × 12 × 12 cm(3); matrix size, 12 × 12 × 12, interpolated to 16 × 16 × 16; acquisition time, 11 minutes 17 seconds) was used. The maximum Cho SNR was assessed in all lesions and correlated with the histopathologic results., Results: Thirty-two malignant and 12 benign lesions were confirmed in 43 patients with histopathologic examination. Seven patients without biopsy underwent imaging follow-up. In 31 of 32 (97%) malignant and 10 of 19 (53%) benign lesions, Cho was detected. The median Cho SNR in malignant lesions was 5.7, compared with 2.0 in benign lesions. With a Cho SNR threshold level of 2.6, 3D MR spectroscopic imaging provided a sensitivity of 97% and a specificity of 84% for the differentiation of benign and malignant breast lesions., Conclusion: At 3T, 3D MR spectroscopic imaging yields high diagnostic sensitivity and specificity for discrimination of benign and malignant breast lesions within reasonable measurement times. This technique allows the study of heterogeneous and multicentric breast tumors and simplifies acquisition planning., (© RSNA, 2011.)

Purpose: We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas., Materials and Methods: Proton magnetic resonance spectroscopic imaging (H-MRSI) with high spatial resolution was performed in 10 glioma patients at 1.5 T. Magnetic resonance spectroscopic imaging (MRSI) data were coregistered to a 3D MR data set used for stereotactic procedures. Metabolite concentrations of choline-containing compounds (Cho), creatine (Cr), and total N-acetyl-aspartate (tNAA) in addition to metabolite ratios of Cho/Cr, tNAA/Cr, and Cho/tNAA were calculated for voxel positions at biopsy loci with low tumor cell infiltration. Metabolite values were correlated with histopathologic findings expressed as a relative (% tumor infiltration, %TI) and an absolute parameter (tumor cell number, TCN)., Results: We found a strong negative linear correlation for tNAA with %TI (R = -0.773, P < 0.001) and TCN (R = -0.769, P < 0.001) but no correlation for Cho (P > 0.05). On the other hand, the metabolite ratio of Cho/Cr showed a moderate positive linear correlation with %TI (R = 0.523, P = 0.012) and TCN (R = 0.486, P = 0.019), but no correlation was obtained for tNAA/Cr (P > 0.05). Differences in correlation between tNAA and Cho as well as tNAA/Cr and Cho/Cr were significant for both %TI (P = 0.012 and P = 0.024) and TCN (P = 0.016 and P = 0.040) using a t test., Conclusions: We conclude that absolute values of tNAA are more significant than Cho in the detection of low tumor cell infiltration. On the basis of absolute metabolite values, neuronal damage seems to be more distinct than cell membrane proliferation in the border zone of gliomas. Furthermore, the calculation of metabolite ratios versus Cr for the border zone may yield to misleading results because Cr is not constant in this area.

Purpose: To evaluate proton magnetic resonance (MR) spectroscopic imaging with high spatial resolution for preoperative grading of suspected World Health Organization grades II and III gliomas., Materials and Methods: Institutional ethics committee approval and informed consent were obtained for control subjects but were not required for the retrospective component involving patients. Twenty-six patients (10 women, 16 men; mean age, 37.5 years) suspected of having gliomas and 26 age- and sex-matched control subjects underwent proton MR spectroscopy. Absolute metabolite concentrations for choline-containing compounds (Cho), creatine (Cr), and N-acetylaspartate (NAA)-N-acetylaspartylglutamate (total NAA [tNAA]) were calculated by using a user-independent spectral fit program. Metabolic maps of Cho/tNAA ratios were calculated, segmented, and used for MR spectroszpcopy-guided stereotactic brain biopsy. Two-sided paired Student t tests were used to test for statistical significance., Results: Significantly lower Cho levels (P = .002) and higher tNAA levels (P = .010) were found in grade II tumors (n = 9) compared with grade III tumors (n = 17). The average Cho/tNAA ratio over the voxels in the tumor center showed a distinct difference (P < .001) between grade II and III gliomas at a threshold of 0.8 (with ratios <0.8 for grade II). The maximum Cr concentration in the tumor showed a clear-cut threshold between grade III oligodendrogliomas and oligoastrocytomas (Cr level, <7 mmol/L) and grade III astrocytomas (Cr level, >7 mmol/L; P = .020). Comparison between the histopathologic findings from the MR spectroscopy-guided biopsy samples (76 biopsies from 26 patients) and molar metabolite values in corresponding voxels located at the biopsy sampling points showed a negative linear correlation for tNAA (r = -0.905) and a positive exponential correlation for Cho (r = 0.769) and Cho/tNAA (r = 0.885)., Conclusion: Proton MR spectroscopic imaging with high spatial resolution allows preoperative grading of gliomas., (Copyright RSNA, 2006.)

Object: It is often difficult to delineate the extent of invasion of high- and low-grade gliomas into normal brain tissue by using conventional T1- and T2-weighted magnetic resonance (MR) imaging. Knowledge of the relationship between the tumor infiltration zone and normal brain, however, is one of the prerequisites for performing as radical a tumor resection as possible. Proton MR spectroscopy allows noninvasive measurements of the concentrations and spatial distributions of brain metabolites and, therefore, may provide biochemical information in vivo, that is useful in distinguishing pathological from normal areas of the brain. The authors have developed a method to use the properties of MR spectroscopy to investigate intraoperatively pathological changes in the spatial distribution of choline (Cho)-containing compounds, total creatine, and N-acetylaspartate (NAA) in brain tumors with the aid of frameless stereotaxy., Methods: Maps of the Cho/NAA ratio were calculated and automatic segmentation of the tumors was performed. Spectroscopic images of the segmented tumor were matched to an anatomical three-dimensional (3D) MR imaging set by applying a fully automated mutual-information algorithm. The resulting 3D MR image can be used subsequently for neurosurgical planning, transfer to a frameless stereotactic system, and display in the navigation microscope during surgery leading to 1H-MR spectroscopy-guided navigation., Conclusions: This method may allow better intraoperative identification of tumor border zones based on metabolic changes due to tumor infiltration.

Rationale and Objectives: This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla., Methods: Short-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data., Results: Metabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated., Conclusions: The authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

In a systematic study on the interdependence of linewidth, signal-to-noise ratio (SNR), and spatial resolution in 3D proton spectroscopic imaging ((1)H-SI) at 3 T, we demonstrate reduced linewidths with increased spatial resolution due to reduced magnetic inhomogeneity within the brain. High-precision quantitative data (0.75-0.094 cm(3)) were obtained for all resolutions, enabling the creation of metabolic maps that display details such as the ventricles, sulci, and gyri. High-resolution (1)H-SI allows differences in metabolic ratios to be estimated for anatomically defined regions in gray (GM) and white matter (WM). Seven distinct regions in a healthy brain were anatomically segmented and their metabolic ratios were compared quantitatively. Data from a tumor patient are also presented to demonstrate potential clinical applications. Because of the high resolution, the metabolite ratios could be determined for distinct pathologic regions within the tumor and its surroundings. The method was additionally applied to a patient with patchy Pelizaeus Merzbacher disease (PMD), and compared to single-voxel spectroscopy performed in the same session. High-resolution SI data were demonstrated in our study to allow the direct matching of anatomic and metabolic images. This may enhance the clinical value of (1)H-SI., (Copyright 2003 Wiley-Liss, Inc.)

In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented DL sodium beta-hydroxybutyrate (beta-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95%) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of beta-OHB increased to levels comparable to a 16- to 24-h fast while on DL sodium beta-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of beta-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of beta-OHB to acetoacetate indicated exogenous origin of beta-OHB. An increase of intracerebral concentrations of beta-OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral DL sodium beta-OHB was tolerated without side effects. This first report on oral supplementation of DL sodium beta-OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood-brain barrier and could provide the basis for further evaluation of the neuroprotective effect of beta-OHB in conditions with hypoketotic hypoglycemia.