Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Prospective motion correction for cervical spinal cord MRS.

PURPOSE: To develop prospective motion correction for single-voxel MRS in the human cervical spinal cord. METHODS: A motion MR navigator was implemented using reduced field-of-view 2D-selective RF excitation together with EPI readout. A short-echo semi-LASER sequence (TE = 30 ms) was updated to incorporate this real-time image-based motion navigator, as well as real-time shim and frequency navigators. Five healthy participants were studied at 3 T with a 64-channel head-neck receive coil. Single-voxel MRS data were measured in a voxel located at the C3-5 vertebrae level. The motion navigator was used to correct for translations in the X-Y plane and was validated by assessing spectral quality with and without prospective correction in the presence of subject motion. RESULTS: Without prospective correction, motion resulted in severe lipid contamination in the MR spectra. With prospective correction, the quality of spinal cord MR spectra in the presence of motion was similar to that obtained in the absence of motion, with comparable spectral signal-to-noise ratio and linewidth and no significant lipid contamination. CONCLUSION: Prospective motion and B0 correction allow acquisition of good-quality MR spectra in the human cervical spinal cord in the presence of motion. This new technique should facilitate reliable acquisition of spinal cord MR spectra in both research and clinical settings.

Fast high-resolution prospective motion correction for single-voxel spectroscopy.

PURPOSE: To develop a fast high-resolution image-based motion correction method using spiral navigators with multislice-to-volume registration. METHODS: A semi-LASER sequence was modified to include a multislice spiral navigator for prospective motion correction (∼305 ms including acquisition, processing, and feedback) as well as shim and frequency navigators for prospective shim and frequency correction (∼100 ms for each). MR spectra were obtained in the prefrontal cortex in five healthy subjects at 3 T with and without prospective motion and shim correction. The effect of key navigator parameters (number of slices, image resolution, and excitation flip angle) on registration accuracy was assessed using simulations. RESULTS: Without prospective motion and shim correction, spectral quality degraded significantly in the presence of voluntary motion. In contrast, with prospective motion and shim correction, spectral quality was improved (metabolite linewidth = 6.7 ± 0.6 Hz, SNR= 67 ± 9) and in good agreement with baseline data without motion (metabolite linewidth = 6.9 ± 0.9 Hz, SNR = 73 ± 9). In addition, there was no significant difference in metabolites concentrations measured without motion and with prospective motion and shim correction in the presence of motion. Simulations showed that the registration precision was comparable when using three navigator slices with 3 mm resolution and when using the entire volume (all slices) with 8 mm resolution. CONCLUSION: The proposed motion correction scheme allows fast and precise prospective motion and shim correction for single-voxel spectroscopy at 3 T. With 3 mm resolution, only a few navigator slices are necessary to achieve excellent motion correction performance.

B0-insensitive image navigators for prospective motion-corrected MRS with localized second-order shimming.

PURPOSE: Localized shimming in single-voxel MRS often results in large B0 inhomogeneity outside the volume-of-interest. This causes unacceptable degradation in motion navigator images. Switching back and forth between whole-brain shim and localized shim is possible for linear shims, but not for higher-order shims. Here we propose motion navigators largely insensitive to B0 inhomogeneity for prospective motion-corrected MRS with localized higher-order shimming. METHODS: A recent fast high-resolution motion navigator based on spiral-in/out k-space trajectories and multislice-to-volume registration was modified by splitting the readout into multiple shot interleaves which shortened the echo time and reduced the effect of B0 inhomogeneity. The performance of motion correction was assessed in healthy subjects in the prefrontal cortex using a sLASER sequence at 3T (N = 5) and 7T (N = 5). RESULTS: With multiple spatial interleaves, excellent quality navigator images were acquired in the whole brain in spite of large B0 inhomogeneity outside the MRS voxel. The total duration of the navigator in sLASER remained relatively short even with multiple shots (3T: 10 spatial interleaves 94 ms per slice; 7T: 15 spatial interleaves 103 ms per slice). Prospective motion correction using the multi-shot navigators yielded comparable spectral quality (water linewidth and metabolite SNR) with and without subject motion. CONCLUSION: B0-insensitive motion navigators enable prospective motion correction for MRS with all first- and second-order shims adjusted in the MRS voxel, providing optimal spectral linewidth.

Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy.

Background Noninvasive identification of glioma subtypes is important for optimizing treatment strategies. Purpose To compare the in vivo neurochemical profiles between isocitrate dehydrogenase (IDH) 1-mutant 1p/19q codeleted gliomas and their noncodeleted counterparts measured by MR spectroscopy at 3.0 T with a point-resolved spectroscopy (PRESS) sequence optimized for D-2-hydroxyglutarate (2HG) detection. Materials and Methods Adults with IDH1-mutant gliomas were retrospectively included for this study from two university hospitals (inclusion period: January 2015 to July 2016 and September 2019 to June 2021, respectively) based on availability of 1p/19q codeletion status and a PRESS acquisition optimized for 2HG detection (echo time, 97 msec) at 3.0 T before any treatment. Spectral analysis was performed using LCModel and a simulated basis set. Metabolite quantification was performed using the water signal as a reference and correcting for water and metabolite longitudinal and transverse relaxation time constants. Concentration ratios were computed using total creatine (tCr) and total choline. A two-tailed unpaired t test was used to compare metabolite concentrations obtained in codeleted versus noncodeleted gliomas, accounting for multiple comparisons. Results Thirty-one adults (mean age, 39 years ± 8 [SD]; 19 male) were included, and 19 metabolites were quantified. Cystathionine concentration was higher in codeleted (n = 13) than noncodeleted (n = 18) gliomas when quantification was performed using the water signal or tCr as references (2.33 mM ± 0.98 vs 0.93 mM ± 0.94, and 0.34 mM ± 0.14 vs 0.14 mM ± 0.14, respectively; both P < .001). The sensitivity and specificity of PRESS to detect codeletion by means of cystathionine quantification were 92% and 61%, respectively. Other metabolites did not show evidence of a difference between groups (P > .05). Conclusion Higher cystathionine levels were detected in IDH1-mutant 1p/19q codeleted gliomas than in their noncodeleted counterparts with use of a PRESS sequence optimized for 2HG detection. Of 19 metabolites quantified, only cystathionine showed evidence of a difference in concentration between groups. Clinical trial registry no. NCT01703962 © RSNA, 2023 See also the editorial by Lin in this issue.

Quantification of GABA concentration measured noninvasively in the human posterior cingulate cortex with 7 T ultra-short-TE MR spectroscopy.

PURPOSE: The increased spectral dispersion achieved at ultra-high field permits quantification of γ-aminobutyric acid (GABA) concentrations at ultra-short-TE without editing. This work investigated the influence of spectral quality and different LCModel fitting approaches on quantification of GABA. Additionally, the sensitivity with which cross-sectional and longitudinal variations in GABA concentrations can be observed was characterized. METHODS: In - vivo spectra were acquired in the posterior cingulate cortex of 10 volunteers at 7 T using a STEAM sequence. Synthetically altered spectra with different levels of GABA signals were used to investigate the reliability of GABA quantification with different LCModel fitting approaches and different realizations of SNR. The synthetically altered spectra were also used to characterize the sensitivity of GABA quantification. RESULTS: The best LCModel fitting approach used stiff spline baseline, no soft constraints, and measured macromolecules in the basis set. With lower SNR, coefficients of variation increased dramatically. Longitudinal and cross-sectional variations in GABA of 10% could be detected with 79 and 48 participants per group, respectively. However, the small cohort may bias the calculation of the coefficients of variation and of the sample size that would be needed to detect variations in GABA. CONCLUSION: Reliable quantification of normal and abnormal GABA concentrations was achieved for high quality 7 T spectra using LCModel fitting.

Vespa: Integrated applications for RF pulse design, spectral simulation and MRS data analysis.

PURPOSE: The Vespa package (Versatile Simulation, Pulses, and Analysis) is described and demonstrated. It provides workflows for developing and optimizing linear combination modeling (LCM) fitting for 1 H MRS data using intuitive graphical user interface interfaces for RF pulse design, spectral simulation, and MRS data analysis. Command line interfaces for embedding workflows in MR manufacturer platforms and utilities for synthetic dataset creation are included. Complete provenance is maintained for all steps in workflows. THEORY AND METHODS: Vespa is written in Python for compatibility across operating systems. It embeds the PyGAMMA spectral simulation library for spectral simulation. Multiprocessing methods accelerate processing and visualization. Applications use the Vespa database for results storage and cross-application access. Three projects demonstrate pulse, sequence, simulation, and data analysis workflows: (1) short TE semi-LASER single-voxel spectroscopy (SVS) LCM fitting, (2) optimizing MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) flip angle and LCM fitting, and (3) creating a synthetic short TE dataset. RESULTS: The LCM workflows for in vivo basis set creation and spectral analysis showed reasonable results for both the short TE semi-LASER and MEGA-PRESS. Examples of pulses, simulations, and data fitting are shown in Vespa application interfaces for various steps to demonstrate the interactive workflow. CONCLUSION: Vespa provides an efficient and extensible platform for characterizing RF pulses, pulse design, spectral simulation optimization, and automated LCM fitting via an interactive platform. Modular design and command line interface make it easy to embed in other platforms. As open source, it is free to the MRS community for use and extension. Vespa source code and documentation are available through GitHub.

Clinically Meaningful Magnetic Resonance Endpoints Sensitive to Preataxic Spinocerebellar Ataxia Types 1 and 3.

OBJECTIVE: This study was undertaken to identify magnetic resonance (MR) metrics that are most sensitive to early changes in the brain in spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3) using an advanced multimodal MR imaging (MRI) protocol in the multisite trial setting. METHODS: SCA1 or SCA3 mutation carriers and controls (n = 107) underwent MR scanning in the US-European READISCA study to obtain structural, diffusion MRI, and MR spectroscopy data using an advanced protocol at 3T. Morphometric, microstructural, and neurochemical metrics were analyzed blinded to diagnosis and compared between preataxic SCA (n = 11 SCA1, n = 28 SCA3), ataxic SCA (n = 14 SCA1, n = 37 SCA3), and control (n = 17) groups using nonparametric testing accounting for multiple comparisons. MR metrics that were most sensitive to preataxic abnormalities were identified using receiver operating characteristic (ROC) analyses. RESULTS: Atrophy and microstructural damage in the brainstem and cerebellar peduncles and neurochemical abnormalities in the pons were prominent in both preataxic groups, when patients did not differ from controls clinically. MR metrics were strongly associated with ataxia symptoms, activities of daily living, and estimated ataxia duration. A neurochemical measure was the most sensitive metric to preataxic changes in SCA1 (ROC area under the curve [AUC] = 0.95), and a microstructural metric was the most sensitive metric to preataxic changes in SCA3 (AUC = 0.92). INTERPRETATION: Changes in cerebellar afferent and efferent pathways underlie the earliest symptoms of both SCAs. MR metrics collected with a harmonized advanced protocol in the multisite trial setting allow detection of disease effects in individuals before ataxia onset with potential clinical trial utility for subject stratification. ANN NEUROL 2022.

Scyllo-inositol: Transverse relaxation time constant at 3 T and concentration changes associated with aging and alcohol use.

The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3 T. Twenty-nine young adults (age 21 ± 1 years) and 24 older adults (age 74 ± 3 years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3 T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.

On the relationship between GABA+ and glutamate across the brain.

Equilibrium between excitation and inhibition (E/I balance) is key to healthy brain function. Conversely, disruption of normal E/I balance has been implicated in a range of central neurological pathologies. Magnetic resonance spectroscopy (MRS) provides a non-invasive means of quantifying in vivo concentrations of excitatory and inhibitory neurotransmitters, which could be used as diagnostic biomarkers. Using the ratio of excitatory and inhibitory neurotransmitters as an index of E/I balance is common practice in MRS work, but recent studies have shown inconsistent evidence for the validity of this proxy. This is underscored by the fact that different measures are often used in calculating E/I balance such as glutamate and Glx (glutamate and glutamine). Here we used a large MRS dataset obtained at ultra-high field (7 T) measured from 193 healthy young adults and focused on two brain regions - prefrontal and occipital cortex - to resolve this inconsistency. We find evidence that there is an inter-individual common ratio between GABA+ (γ-aminobutyric acid and macromolecules) and Glx in the occipital, but not prefrontal cortex. We further replicate the prefrontal result in a legacy dataset (n = 78) measured at high-field (3 T) strength. By contrast, with ultra-high field MRS data, we find extreme evidence that there is a common ratio between GABA+ and glutamate in both prefrontal and occipital cortices, which cannot be explained by participant demographics, signal quality, fractional tissue volume, or other metabolite concentrations. These results are consistent with previous electrophysiological and theoretical work supporting E/I balance. Our findings indicate that MRS-detected GABA+ and glutamate (but not Glx), are a reliable measure of E/I balance .

Results and interpretation of a fitting challenge for MR spectroscopy set up by the MRS study group of ISMRM.

PURPOSE: Fitting of MRS data plays an important role in the quantification of metabolite concentrations. Many different spectral fitting packages are used by the MRS community. A fitting challenge was set up to allow comparison of fitting methods on the basis of performance and robustness. METHODS: Synthetic data were generated for 28 datasets. Short-echo time PRESS spectra were simulated using ideal pulses for the common metabolites at mostly near-normal brain concentrations. Macromolecular contributions were also included. Modulations of signal-to-noise ratio (SNR); lineshape type and width; concentrations of γ-aminobutyric acid, glutathione, and macromolecules; and inclusion of artifacts and lipid signals to mimic tumor spectra were included as challenges to be coped with. RESULTS: Twenty-six submissions were evaluated. Visually, most fit packages performed well with mostly noise-like residuals. However, striking differences in fit performance were found with bias problems also evident for well-known packages. In addition, often error bounds were not appropriately estimated and deduced confidence limits misleading. Soft constraints as used in LCModel were found to substantially influence the fitting results and their dependence on SNR. CONCLUSIONS: Substantial differences were found for accuracy and precision of fit results obtained by the multiple fit packages.

The influence of cystathionine on neurochemical quantification in brain tumor in vivo MR spectroscopy.

PURPOSE: To evaluate the ability of the PRESS sequence (TE  = 97 ms, optimized for 2-hydroxyglutarate detection) to detect cystathionine in gliomas and the effect of the omission of cystathionine on the quantification of the full neurochemical profile. METHODS: Twenty-three subjects with a glioma were retrospectively included based on the availability of both MEGA-PRESS and PRESS acquisitions at 3T, and the presence of the cystathionine signal in the edited MR spectrum. In eight subjects, the PRESS acquisition was performed also in normal tissue. Metabolite quantification was performed using LCModel and simulated basis sets. The LCModel analysis for the PRESS data was performed with and without cystathionine. RESULTS: All subjects with glioma had detectable cystathionine levels >1 mM with Cramér-Rao lower bounds (CRLB) <15%. The mean cystathionine concentrations were 3.49 ± 1.17 mM for MEGA-PRESS and 2.20 ± 0.80 mM for PRESS data. Cystathionine concentrations showed a significant correlation between the two MRS methods (r = 0.58, p = .004), and it was not detectable in normal tissue. Using PRESS, 19 metabolites were quantified with CRLB <50% for more than half of the subjects. The metabolites that were significantly (p < .0028) and mostly affected by the omission of cystathionine were aspartate, betaine, citrate, γ-aminobutyric acid (GABA), and serine. CONCLUSIONS: Cystathionine was detectable by PRESS in all the selected gliomas, while it was not detectable in normal tissue. The omission from the spectral analysis of cystathionine led to severe biases in the quantification of other neurochemicals that may play key roles in cancer metabolism.

Broadband selective excitation radiofrequency pulses for optimized localization in vivo.

PURPOSE: The aim of the study is to optimize the performance of localized 1 H MRS sequences at 3T, using the entire spin system of N-acetyl aspartate (NAA) as an example of the large chemical shift spread of all the metabolites routinely detected in vivo, including the amide region. We specifically focus on the design of the suitable broadband excitation radiofrequency (RF) pulses to minimize chemical shift artifacts. METHODS: The performance of the excitation and refocusing pulse shapes is evaluated with respect to NAA localization. Two new excitation RF pulses are developed to achieve optimized performance in the brain using single-voxel 1 H MRS at 3T. Numerical simulations and in vivo experiments are carried out to demonstrate the performance of the RF pulses. RESULTS: New excitation RF pulses with the same B1 requirements but larger excitation bandwidth (up to a factor of 2) are shown to significantly reduce localization artifacts. The large frequency spread of the entire NAA spin system necessitates the use of broadband excitation and refocusing pulses for MRS at 3T. CONCLUSION: To minimize chemical shift artifacts of metabolic compounds with spins in the amide area (>5 ppm) at 3T it is important to use broadband excitation and refocusing pulses.

Plug-and-play advanced magnetic resonance spectroscopy.

PURPOSE: Advanced MRS protocols improve data quality and reproducibility relative to vendor-provided protocols; however, they are challenging to incorporate into the clinical workflow and require local MRS expertise for successful implementation. Here, we developed an automated advanced MRS acquisition protocol at 3T to facilitate acquisition of high-quality spectroscopic data without local MRS expertise. METHODS: First, a B0 shimming protocol was selected for automation by comparing 3 widely used B0 algorithms (2 vendor protocols and FAST(EST)MAP). Next, voxel-based B0 and B1 calibrations were incorporated into the consensus-recommended semi-LASER sequence and combined with an automated VOI prescription tool, a recently developed method for automated voxel prescription. The efficiency of collecting single-voxel data from a clinical cohort (N = 40) with the automated protocol (calibration time and fraction of usable datasets) was compared with the nonautomated semi-LASER protocol (N = 35) whereby all prescan calibrations were executed manually in the academic hospital setting with rotating MR technologists in the neuroradiology unit. RESULTS: A multi-iteration FAST(EST)MAP protocol resulted in narrower water linewidths than vendor's B0 shim protocols for data acquired from 6 brain locations (p < 1e-5) and was selected for automation. The automated B0 and B1 calibrations resulted in a time saving of ~4.5 minutes per voxel relative to the same advanced protocol executed manually. All spectra acquired with the automated protocol were usable, whereas only 86% of those collected with the manual protocol were usable and spectral quality was more variable. CONCLUSION: The plug-and-play advanced MRS protocol allows automated acquisition of high-quality MRS data with high success rate and consistency on a clinical 3T platform.

In vivo 1 H MR spectroscopy with J-refocusing.

PURPOSE: The goal of this study was to propose a novel localized proton MR spectroscopy (MRS) sequence that reduces signal loss due to J-modulation in the rat brain in vivo. METHODS: Sprague-Dawley rats were studied at 9.4 T. A semi-LASER sequence with evenly distributed echo-time (TE ) was used, and a 90° J-refocusing pulse was inserted at TE /2. Proton spectra were acquired at two TE s (30 and 68 ms), with and without the J-refocused pulse. Data were processed in MATLAB and quantified with LCModel. RESULTS: The J-refocused spectrum acquired at TE = 30 ms did not show any signal losses due to J-modulation and had comparable spectral pattern to the one acquired with semi-LASER using the minimum achievable TE . Higher signal amplitudes for glutamine, γ-aminobutyric acid and glutathione led to more reliable quantification precision for these metabolites. The refocused signal intensities at TE = 68 ms were also unaffected by J-modulation but were smaller than the signals at TE = 30 ms mainly due to transverse T2 relaxation of metabolites. CONCLUSION: The proposed localized MRS sequence will be beneficial in both animal and human MRS studies when using ultra-short TE is not possible while also providing more reliable quantification precision for J-coupled metabolites.

MEGA-PRESS of GABA+: Influences of acquisition parameters.

γ-aminobutyric acid (GABA) was the first molecule that was edited with MEGA-PRESS. GABA edited spectroscopy is challenged by limited selectivity of editing pulses. Coediting of resonances from macromolecules (MM) is the greatest single limitation of GABA edited spectroscopy. In this contribution, relative signal contributions from GABA, MM and homocarnosine to the total MEGA-PRESS edited signal at ~3 ppm, i.e., GABA+, are simulated at 3 tesla using several acquisition schemes. The base scheme is modeled after those currently supplied by vendors: it uses typical pulse shapes and lengths, it minimizes the first echo time (TE), and the delay between the editing pulses is kept at TE/2. Edited spectra are simulated for imperfect acquisition parameters such as incorrect frequency, larger chemical shift displacement, incorrect transmit B1 -field calibration for localization and editing pulses, and longer TE. An alternative timing scheme and longer editing pulses are also considered. Additional simulations are performed for symmetric editing around the MM frequency to suppress the MM signal. The relative influences of these acquisition parameters on the constituents of GABA+ are examined from the perspective of modern experimental designs for investigating brain GABA concentration differences in healthy and diseased humans. Other factors that influence signal contributions, such as T1 and T2 relaxation times are also considered.

Water and lipid suppression techniques for advanced 1 H MRS and MRSI of the human brain: Experts' consensus recommendations.

The neurochemical information provided by proton magnetic resonance spectroscopy (MRS) or MR spectroscopic imaging (MRSI) can be severely compromised if strong signals originating from brain water and extracranial lipids are not properly suppressed. The authors of this paper present an overview of advanced water/lipid-suppression techniques and describe their advantages and disadvantages. Moreover, they provide recommendations for choosing the most appropriate techniques for proper use. Methods of water signal handling are primarily focused on the VAPOR technique and on MRS without water suppression (metabolite cycling). The section on lipid-suppression methods in MRSI is divided into three parts. First, lipid-suppression techniques that can be implemented on most clinical MR scanners (volume preselection, outer-volume suppression, selective lipid suppression) are described. Second, lipid-suppression techniques utilizing the combination of k-space filtering, high spatial resolutions and lipid regularization are presented. Finally, three promising new lipid-suppression techniques, which require special hardware (a multi-channel transmit system for dynamic B1+ shimming, a dedicated second-order gradient system or an outer volume crusher coil) are introduced.

Across-vendor standardization of semi-LASER for single-voxel MRS at 3T.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 µT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 µT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.

Advanced single voxel 1 H magnetic resonance spectroscopy techniques in humans: Experts' consensus recommendations.

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections.

In vivo 1 H MRS detection of cystathionine in human brain tumors.

PURPOSE: To report the technical aspects of noninvasive detection of cystathionine in human brain glioma with edited MRS, and to investigate possible further acquisition improvements for robust quantification of this metabolite. METHODS: In vivo 1 H MR spectra were acquired at 3 T in 15 participants with an isocitrate dehydrogenase-mutated glioma using a MEGA-PRESS (MEscher GArwood point resolved spectroscopy) sequence previously employed for 2-hydroxyglutarate detection (TR = 2 s, TE = 68 ms). The editing pulse was applied at 1.9 ppm for the edit-on condition and at 7.5 ppm for the edit-off condition. To evaluate the editing efficiency, spectra were acquired in 1 participant by placing the editing pulse for the edit-on condition at 1.9, 2.03, and 2.16 ppm. Cystathionine concentration was quantified using LCModel and a simulated basis set. To confirm chemical shifts and J-coupling values of cystathionine, the 1 H NMR cystathionine spectrum was measured using a high-resolution 500 MHz spectrometer. RESULTS: In 12 gliomas, cystathionine was observed in the in vivo edited MR spectra at 2.72 and 3.85 ppm and quantified. The signal intensity of the cystathionine resonance at 2.72 ppm increased 1.7 and 2.13 times when the editing pulse was moved to 2.03 and 2.16 ppm, respectively. Cystathionine was not detectable in normal brain tissue. CONCLUSION: Cystathionine can be detected in vivo by edited MRS using the same protocol as for 2-hydroxyglutarate detection. This finding may enable a more accurate, noninvasive investigation of cellular metabolism in glioma.