High-Resolution Motion-corrected 7.0-T MRI to Derive Morphologic Measures from the Human Cerebellum in Vivo.

Background The human cerebellum has a large, highly folded cortical sheet. Its visualization is important for various disorders, including multiple sclerosis and spinocerebellar ataxias. The derivation of the cerebellar cortical surface in vivo is impeded by its high foliation. Purpose To image the cerebellar cortex, including its foliations and lamination, in less than 20 minutes, reconstruct the cerebellocortical surface, and extract cortical measures with use of motion-corrected, high-spatial-resolution 7.0-T MRI. Materials and Methods In this prospective study, conducted between February 2021 and July 2022, healthy participants underwent an examination with either a 0.19 × 0.19 × 0.5-mm3, motion-corrected fast low-angle shot (FLASH) sequence (14.5 minutes) or a whole-cerebellum 0.4 × 0.4 × 0.4-mm3, motion-corrected magnetization-prepared 2 rapid gradient-echo (MP2RAGE) sequence (18.5 minutes) at 7.0 T. Four participants underwent an additional FLASH sequence without motion correction. FLASH and MP2RAGE sequences were used to visualize the cerebellar cortical layers, derive cerebellar gray and white matter segmentations, and examine their fidelity. Quantitative measures were compared using repeated-measures analyses of variance or paired t tests. Results Nine participants (median age, 36 years [IQR, 25-42 years; range, 21-62 years]; five women) underwent examination with the FLASH sequence. Nine participants (median age, 37 years [IQR, 34-42 years; range, 25-62 years]; five men) underwent examination with the MP2RAGE sequence. A susceptibility difference between the expected location of the granular and molecular cerebellar layers was visually detected in the FLASH data in all participants. The segmentations derived from the whole-cerebellum MP2RAGE sequence showed the characteristic anatomic features of the cerebellum, like the transverse fissures and splitting folds. The cortical surface area (median, 949 cm2 [IQR, 825-1021 cm2]) was 1.8 times larger, and the cortical thickness (median, 0.88 mm [IQR, 0.81-0.93 mm]) was five times thinner than previous in vivo estimates and closer to ex vivo reference data. Conclusion In vivo imaging of the cerebellar cortical layers and surface and derivation of quantitative measures was feasible in a clinically acceptable acquisition time with use of motion-corrected 7.0-T MRI. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Dietrich in this issue.

Improved detection limits of J-coupled neurometabolites in the human brain at 7 T with a J-refocused sLASER sequence.

In a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo time (TE)-dependent modulation of the signal amplitude and signal loss in the case of overlapping multiplet resonances. This has an adverse effect on quantification of several important metabolites such as glutamate and glutamine. Here, we propose a J-refocused variant of the sLASER sequence (J-sLASER) to improve quantification of J-coupled metabolites at ultrahigh field (UHF). The use of the sLASER sequence is particularly advantageous at UHF as it minimizes chemical shift displacement error and results in relatively homogenous refocusing. We simulated the MRS signal from brain metabolites over a broad range of TE values with sLASER and J-sLASER, and showed that the signal of J-coupled metabolites was increased with J-sLASER with TE values up to ~80 ms. We further simulated "brain-like" spectra with both sequences at the shortest TE available on our scanner. We showed that, despite the slightly longer TE, the J-sLASER sequence results in significantly lower Cramer-Rao lower bounds (CRLBs) for J-coupled metabolites compared with those obtained with sLASER. Following phantom validation, we acquired spectra from two brain regions in 10 healthy volunteers (age 38 ± 15 years) using both sequences. We showed that using J-sLASER results in a decrease of CRLBs for J-coupled metabolites. In particular, we measured a robust ~38% decrease in the mean CRLB (glutamine) in parietal white matter and posterior cingulate cortex (PCC). We further showed, in 10 additional healthy volunteers (age 34 ± 15 years), that metabolite quantification following two separate acquisitions with J-sLASER in the PCC was repeatable. The improvement in quantification of glutamine may in turn improve the independent quantification of glutamate, the main excitatory neurotransmitter in the brain, and will simultaneously help to track possible modulations of glutamine, which is a key player in the glutamatergic cycle in astrocytes.

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.

Background: Antipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis. Aims: This investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine. Materials and Equipment: Antipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment. Outcome Measures: The primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes. Anticipated Results: We hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning. Perspectives: By combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04789915].

Proton metabolic mapping of the brain at 7 T using a two-dimensional free induction decay-echo-planar spectroscopic imaging readout with lipid suppression.

The increased signal-to-noise ratio (SNR) and chemical shift dispersion at high magnetic fields (≥7 T) have enabled neuro-metabolic imaging at high spatial resolutions. To avoid very long acquisition times with conventional magnetic resonance spectroscopic imaging (MRSI) phase-encoding schemes, solutions such as pulse-acquire or free induction decay (FID) sequences with short repetition time and inner volume selection methods with acceleration (echo-planar spectroscopic imaging [EPSI]), have been proposed. With the inner volume selection methods, limited spatial coverage of the brain and long echo times may still impede clinical implementation. FID-MRSI sequences benefit from a short echo time and have a high SNR per time unit; however, contamination from strong extra-cranial lipid signals remains a problem that can hinder correct metabolite quantification. L2-regularization can be applied to remove lipid signals in cases with high spatial resolution and accurate prior knowledge. In this work, we developed an accelerated two-dimensional (2D) FID-MRSI sequence using an echo-planar readout and investigated the performance of lipid suppression by L2-regularization, an external crusher coil, and the combination of these two methods to compare the resulting spectral quality in three subjects. The reduction factor of lipid suppression using the crusher coil alone varies from 2 to 7 in the lipid region of the brain boundary. For the combination of the two methods, the average lipid area inside the brain was reduced by 2% to 38% compared with that of unsuppressed lipids, depending on the subject's region of interest. 2D FID-EPSI with external lipid crushing and L2-regularization provides high in-plane coverage and is suitable for investigating brain metabolite distributions at high fields.

Identifying the source of spurious signals caused by B0 inhomogeneities in single-voxel 1 H MRS.

PURPOSE: Single-voxel MRS (SV MRS) requires robust volume localization as well as optimized crusher and phase-cycling schemes to reduce artifacts arising from signal outside the volume of interest. However, due to local magnetic field gradients (B0 inhomogeneities), signal that was dephased by the crusher gradients during acquisition might rephase, leading to artifacts in the spectrum. Here, we analyzed this mechanism, aiming to identify the source of signals arising from unwanted coherence pathways (spurious signals) in SV MRS from a B0 map. METHODS: We investigated all possible coherence pathways associated with imperfect localization in a semi-localized by adiabatic selective refocusing (semi-LASER) sequence for potential rephasing of signals arising from unwanted coherence pathways by a local magnetic field gradient. We searched for locations in the B0 map where the signal dephasing due to external (crusher) and internal (B0 ) field gradients canceled out. To confirm the mechanism, SV-MR spectra (TE = 31 ms) and 3D-CSI data with the same volume localization as the SV experiments were acquired from a phantom and 2 healthy volunteers. RESULTS: Our analysis revealed that potential sources of spurious signals were scattered over multiple locations throughout the brain. This was confirmed by 3D-CSI data. Moreover, we showed that the number of potential locations where spurious signals could originate from monotonically decreases with crusher strength. CONCLUSION: We proposed a method to identify the source of spurious signals in SV 1 H MRS using a B0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts.

Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction. OBJECTIVES: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD. METHODS: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNRMTw ) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNRMTw and severity of nonmotor symptoms. RESULTS: Mean CNRMTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNRMTw was confined to the right mid-caudal LC and linked regional CNRMTw to nonmotor symptoms. CNRMTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNRMTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms. CONCLUSION: A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

B0 shimming for in vivo magnetic resonance spectroscopy: Experts' consensus recommendations.

Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) allow the chemical analysis of physiological processes in vivo and provide powerful tools in the life sciences and for clinical diagnostics. Excellent homogeneity of the static B0 magnetic field over the object of interest is essential for achieving high-quality spectral results and quantitative metabolic measurements. The experimental minimization of B0 variation is performed in a process called B0 shimming. In this article, we summarize the concepts of B0 field shimming using spherical harmonic shimming techniques, specific strategies for B0 homogenization and crucial factors to consider for implementation and use in both brain and body. In addition, experts' recommendations are provided for minimum requirements for B0 shim hardware and evaluation criteria for the primary outcome of adequate B0 shimming for MRS and MRSI, such as the water spectroscopic linewidth.

Feasibility of Glutamate and GABA Detection in Pons and Thalamus at 3T and 7T by Proton Magnetic Resonance Spectroscopy.

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy (1H-MRS) after an intervention is of interest for studying various brain disorders. However, 1H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) (p < 0.001), lower linewidth (p = 0.001) and lower Cramér-Rao lower bounds (CRLB) (p < 0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T (p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is advantageous for future investigations of excitatory-inhibitory mechanisms in brain disorders.

MR spectroscopy using static higher order shimming with dynamic linear terms (HOS-DLT) for improved water suppression, interleaved MRS-fMRI, and navigator-based motion correction at 7T.

PURPOSE: To interleave global and local higher order shimming for single voxel MRS. Single voxel MR spectroscopy requires optimization of the B0 field homogeneity in the region of the voxel to obtain a narrow linewidth and provide high data quality. However, the optimization of local higher order fields on a localized MRS voxel typically leads to large field offsets outside that volume. This compromises interleaved MR sequence elements that benefit from global field homogeneity such as water suppression, interleaved MRS-fMRI, and MR motion correction. METHODS: A shimming algorithm was developed to optimize the MRS voxel homogeneity and the whole brain homogeneity for interleaved sequence elements, using static higher order shims and dynamic linear terms (HOS-DLT). Shimming performance was evaluated using 6 brain regions and 10 subjects. Furthermore, the benefits of HOS-DLT was demonstrated for water suppression, MRS-fMRI, and motion corrected MRS using fat-navigators. RESULTS: The HOS-DLT algorithm was shown to improve the whole brain homogeneity compared to an MRS voxel-based shim, without compromising the MRS voxel homogeneity. Improved water suppression over the brain, reduced image distortions in MRS-fMRI, and improved quality of motion navigators were demonstrated using the HOS-DLT method. CONCLUSION: HOS-DLT shimming allowed for both local and global field homogeneity, providing excellent MR spectroscopy data quality, as well as good field homogeneity for interleaved sequence elements, even without the need for dynamic higher order shimming capabilities.

Gamma-aminobutyric acid edited echo-planar spectroscopic imaging (EPSI) with MEGA-sLASER at 7T.

PURPOSE: For rapid spatial mapping of gamma-aminobutyric acid (GABA) at the increased sensitivity and spectral separation for ultra-high magnetic field strength (7 tesla [T]), an accelerated edited magnetic resonance spectroscopic imaging technique was developed and optimized for the human brain at 7 T. METHODS: A MEGA-sLASER sequence was used for GABA editing and volume selection to maximize editing efficiency and minimize chemical shift displacement errors. To accommodate the high bandwidth requirements at 7 T, a single-shot echo planar readout was used for rapid simultaneous encoding of the temporal dimension and 1 spatial. B0 and B1 field aspects specific for 7 T were studied together with correction procedures, and feasibility of the EPSI MEGA-sLASER technique was tested in vivo in 5 healthy subjects. RESULTS: Localized edited spectra could be measured in all subjects giving spatial GABA signal distributions over a central brain region, having 45- to 50-Hz spatial intervoxel B0 field variations and up to 30% B1 field deviations. MEGA editing was found unaffected by the B0 inhomogeneities for the optimized sequence. The correction procedures reduced effects of intervoxel B0 inhomogeneities, corrected for spatial editing efficiency variations, and compensated for GABA resonance phase and frequency shifts from subtle motion and acquisition instabilities. The optimized oscillating echo-planar gradient scheme permitted full spectral acquisition at 7 T and exhibited minimal spectral-spatial ghosting effects for the selected brain region. CONCLUSION: The EPSI MEGA-sLASER technique was shown to provide time-efficient mapping of regional variations in cerebral GABA in a central volume of interest with spatial B1 and B0 field variations typical for 7 T.

1 H-MRS processing parameters affect metabolite quantification: The urgent need for uniform and transparent standardization.

Proton magnetic resonance spectroscopy (1 H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of 1 H-MRS metabolite quantification. It is currently unknown to what extent variations in the analysis pipeline used to quantify 1 H-MRS data affect outcomes. The purpose of this study was to evaluate whether the quantification of identical 1 H-MRS scans across independent and experienced research groups would yield comparable results. We investigated the influence of model parameters and spectral quantification software on fitted metabolite concentration values. Sixty spectra in 30 individuals (repeated measures) were acquired using a 7-T MRI scanner. Data were processed by four independent research groups with the freedom to choose their own individualized and optimal parameter settings using LCModel software. Data were processed a second time in one group using an independent software package (NMRWizard) for an additional comparison with a different post-processing platform. Correlations across research groups of the ratio between the highest and, arguably, the most relevant resonances for neurotransmission [N-acetyl aspartate (NAA), N-acetyl aspartyl glutamate (NAAG) and Glu] over the total creatine [creatine (Cr) + phosphocreatine (PCr)] concentration, using Pearson's product-moment correlation coefficient (r), were calculated. Mean inter-group correlations using LCModel software were 0.87, 0.88 and 0.77 for NAA/Cr + PCr, NAA + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. The mean correlations when comparing NMRWizard results with LCModel fitting results at University Medical Center Utrecht (UMCU) were 0.87, 0.89 and 0.71 for NAA/Cr + PCr, NAA + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical 1 H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results reinforce the notion that standard practices should be established to regularize outcomes of 1 H-MRS studies, and that basis sets used for processing should be made available to the scientific community.

Detection of Glutamate Alterations in the Human Brain Using 1H-MRS: Comparison of STEAM and sLASER at 7 T.

PURPOSE: To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) 1H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths. A sLASER sequence has been developed for 7 T, using field focusing at short TE, resulting in twice as much signal as can be obtained using STEAM and improved localization accuracy due to a decreased chemical shift artifact. MATERIALS AND METHODS: Eight subjects were scanned twice using both STEAM and sLASER. Data were acquired from the frontal and occipital brain region. Subsequently, intraclass correlations were computed for the estimated metabolite concentrations. RESULTS: sLASER has higher ICC's for glutamate concentration as compared to STEAM in both the frontal and occipital VOI, which is probably due to the higher sensitivity and localization accuracy. CONCLUSION: We conclude that sLASER 1H-MRS at 7 T is a reliable method to obtain reproducible measures of glutamate levels in the human brain at such high accuracy that individual variability, even between age-matched subjects, is measured.

7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings.

BACKGROUND: The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. METHODS: Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. RESULTS: Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia. CONCLUSIONS: Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives.

Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T.

In vivo water- and fat-suppressed 1 H magnetic resonance spectroscopy (MRS) and 31 P magnetic resonance adiabatic multi-echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of 31 P metabolites were determined, and the reproducibility of 1 H and 31 P MRS was investigated. The transverse relaxation times for phosphoethanolamine (PE) and phosphocholine (PC) were fitted bi-exponentially, with an added short T2 component of 20 ms for adenosine monophosphate, resulting in values of 199 ± 8 and 239 ± 14 ms, respectively. The transverse relaxation time for glycerophosphocholine (GPC) was also fitted bi-exponentially, with an added short T2 component of 20 ms for glycerophosphatidylethanolamine, which resonates at a similar frequency, resulting in a value of 177 ± 6 ms. Transverse relaxation times for inorganic phosphate, γ-ATP and glycerophosphatidylcholine mobile phospholipid were fitted mono-exponentially, resulting in values of 180 ± 4, 19 ± 3 and 20 ± 4 ms, respectively. Coefficients of variation for the duplicate determinations of 1 H total choline (tChol) and the 31 P metabolites were calculated for the group of volunteers. The reproducibility of inorganic phosphate, the sum of phosphomonoesters and the sum of phosphodiesters with 31 P MRS imaging was superior to the reproducibility of 1 H MRS for tChol. 1 H and 31 P data were combined to calculate estimates of the absolute concentrations of PC, GPC and PE in healthy fibroglandular tissue, resulting in upper limits of 0.1, 0.1 and 0.2 mmol/kg of tissue, respectively.

Dual-volume excitation and parallel reconstruction for J-difference-edited MR spectroscopy.

PURPOSE: To develop J-difference editing with parallel reconstruction in accelerated multivoxel (PRIAM) for simultaneous measurement in two separate brain regions of γ-aminobutyric acid (GABA) or glutathione. METHODS: PRIAM separates signals from two simultaneously excited voxels using receiver-coil sensitivity profiles. PRIAM was implemented into Mescher-Garwood (MEGA) edited experiments at 3 Tesla (T), and validated by acquiring dual-voxel MEGA-PRIAM (and compared with conventional single-voxel MEGA-PRESS) spectra from a GABA/glutathione phantom, and 11 healthy participants. RESULTS: MEGA-PRIAM effectively separated phantom spectra with ∼3-4% between-voxel contamination. GABA and glutathione measurements agreed well with those obtained using single-voxel MEGA-PRESS (mean difference was below 2% in GABA levels, and below 7% in glutathione levels). In vivo, GABA- and glutathione-edited spectra were successfully reconstructed with a mean in vivo g-factor of 1.025 (typical voxel-center separation: 7-8 cm). MEGA-PRIAM experiments showed higher signal-to-noise ratio than sequential single-voxel experiments of the same total duration (mean improvement 1.38 ± 0.24). CONCLUSIONS: Simultaneous acquisition of J-difference-edited GABA or glutathione spectra from two voxels is feasible at 3 T. MEGA-PRIAM increases data acquisition rates compared with MEGA-PRESS by a factor of 2. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

A comparison of navigators, snap-shot field monitoring, and probe-based field model training for correcting B0 -induced artifacts in T2*-weighted images at 7 T.

PURPOSE: To compare methods for estimating B0 maps used in retrospective correction of high-resolution anatomical images at ultra-high field strength. The B0 maps were obtained using three methods: (1) 1D navigators and coil sensitivities, (2) field probe (FP) data and a low-order spherical harmonics model, and (3) FP data and a training-based model. METHODS: Data from nine subjects were acquired while they performed activities inducing B0 field fluctuations. Estimated B0 fields were compared with reference data, and the reductions of artifacts were compared in corrected T2* images. RESULTS: Reduction of sum-of-squares difference relative to a reference image was evaluated, and Method 1 yielded the largest artifact reduction: 27 ± 15%, 20 ± 18% (mean ± 1 standard deviation) for deep breathing and combined deep breathing and hand motion activities. Method 3 performed almost as well (24 ± 18%, 15 ± 17%), provided that adequate training data were used, and Method 2 gave a similar result (21 ± 16%, 19 ± 17%). CONCLUSION: This study confirms that all of the investigated methods can be used in retrospective image correction. In terms of image quality, Method 1 had a small advantage, whereas the FP-based methods measured the B0 field slightly more accurately. The specific strengths and weaknesses of FPs and navigators should therefore be considered when determining which B0 -estimation method to use. Magn Reson Med 78:1373-1382, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Erratum to: Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra-individual comparison study.

[This corrects the article DOI: 10.1186/s40064-015-1654-7.].

Prospective frequency correction for macromolecule-suppressed GABA editing at 3T.

PURPOSE: To investigate the effects of B0 field offsets and drift on macromolecule (MM)-suppressed GABA-editing experiments, and to implement and test a prospective correction scheme. "Symmetric" editing schemes are proposed to suppress unwanted coedited MM signals in GABA editing. MATERIALS AND METHODS: Full density-matrix simulations of both conventional (nonsymmetric) and symmetric MM-suppressed editing schemes were performed for the GABA spin system to evaluate their offset-dependence. Phantom and in vivo (15 subjects at 3T) GABA-edited experiments with symmetrical suppression of MM signals were performed to quantify the effects of field offsets on the total GABA+MM signal (designated GABA+). A prospective frequency correction method based on interleaved water referencing (IWR) acquisitions was implemented and its experimental performance evaluated during positive and negative drift. RESULTS: Simulations show that the signal from MM-suppressed symmetrical editing schemes is an order of magnitude more susceptible to field offsets than the signal from nonsymmetric editing schemes. The MM-suppressed GABA signal changes by 8.6% per Hz for small field offsets. IWR significantly reduces variance in the field offset and measured GABA levels (both P < 0.001 by F-tests), maintaining symmetric suppression of MM signal. CONCLUSION: Symmetrical editing schemes substantially increase the dependence of measurements on B0 field offsets, which can arise due to patient movement and/or scanner instability. It is recommended that symmetrical editing should be used in combination with effective B0 stabilization, such as that provided by IWR. J. Magn. Reson. Imaging 2016;44:1474-1482.

Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra-individual comparison study.

The aim of this study is to compare the current state of lesion identification, the BI-RADS classification and the contrast-enhancement behavior at 7T and 3T breast MRI in the same patient group. Twenty-seven patients with thirty suspicious lesions were selected for this prospective study and underwent both 7T and 3T MRI. All examinations were rated by two radiologists (R1 and R2) independently on image quality, lesion identification and BI-RADS classification. We assessed sensitivity, specificity, NPV and PPV, observer agreement, lesion sizes, and contrast-enhancement-to-noise ratios (CENRs) of mass lesions. Fifteen of seventeen histopathological proven malignant lesions were detected at both field strengths. Image quality of the dynamic series was good at 7T, and excellent at 3T (P = 0.001 for R1 and P = 0.88 for R2). R1 found higher rates of specificity, NPV and PPV at 7T when compared to 3T, while R2 found the same results for sensitivity, specificity, NPV and PPV for both field strengths. The observers showed excellent agreement for BI-RADS categories at 7T (κ = 0.86) and 3T (κ = 0.93). CENRs were higher at 7T (P = 0.015). Lesion sizes were bigger at 7T according to R2 (P = 0.039). Our comparison study shows that 7T MRI allows BI-RADS conform analysis. Technical improvements, such as acquisition of T2w sequences and adjustment of B1+ field inhomogeneity, are still necessary to allow clinical use of 7T breast MRI.

Proton observed phosphorus editing (POPE) for in vivo detection of phospholipid metabolites.

The purpose of this article was to compare the sensitivity of proton observed phosphorus editing (POPE) with direct (31) P MRS with Ernst angle excitation for (1) H-(31) P coupled metabolites at 7 T. POPE sequences were developed for detecting phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) on the (1) H channel, thereby using the enhanced sensitivity of the (1) H nuclei over (31) P detection. Five healthy volunteers were examined with POPE and (31) P-MRS. POPE editing showed a more than doubled sensitivity in an ideal phantom experiment as compared with direct (31) P MRS with Ernst angle excitation. In vivo, despite increased relaxation losses, significant gains in signal-to-noise ratio (SNR) of 30-40% were shown for PE and GPE + PC levels in the human brain. The SNR of GPC was lower in the POPE measurement compared with the (31) P-MRS measurement. Furthermore, selective narrowband editing on the (31) P channel showed the ability to separate the overlapping GPE and PE signals in the (1) H spectrum. POPE can be used for enhanced detection of (1) H-(31) P coupled metabolites in vivo. Copyright © 2015 John Wiley & Sons, Ltd.