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Purpose: T 1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T 1 mapping technique, using acquisition details from a seminal T 1 mapping paper on a standardized phantom and in human brains., Methods: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T 1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed., Results: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org., Conclusion: The T 1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T 1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T 1 variations in vivo., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Frequency drift correction is an important postprocessing step in MRS that yields improvements in spectral quality and metabolite quantification. Although routinely applied in single-voxel MRS, drift correction is much more challenging in MRSI due to the presence of phase-encoding gradients. Thus, separately acquired navigator scans are normally required for drift estimation. In this work, we demonstrate the use of self-navigating rosette MRSI trajectories combined with time-domain spectral registration to enable retrospective frequency drift corrections without the need for separately acquired navigator echoes., Methods: A rosette MRSI sequence was implemented to acquire data from the brains of 5 healthy volunteers. FIDs from the center of k-space ( k = 0 $$ k=0 $$ FIDs) were isolated from each shot of the rosette acquisition, and time-domain spectral registration was used to estimate the frequency offset of each k = 0 $$ k=0 $$ FID relative to a reference scan (the first k = 0 $$ k=0 $$ FID in the series). The estimated frequency offsets were then used to apply corrections throughout k $$ k $$ -space. Improvements in spectral quality were assessed before and after drift correction., Results: Spectral registration resulted in significant improvements in signal-to-noise ratio (12.9%) and spectral linewidths (18.5%). Metabolite quantification was performed using LCModel, and the average Cramer-Rao lower bounds uncertainty estimates were reduced by 5.0% for all metabolites, following field drift correction., Conclusion: This study demonstrated the use of self-navigating rosette MRSI trajectories to retrospectively correct frequency drift errors in in vivo MRSI data. This correction yields meaningful improvements in spectral quality., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: The spin-echo, full-intensity acquired localized (SPECIAL) sequence is a method for single-voxel, localized MRS in vivo with short TEs. In this study we modified the SPECIAL sequence to simultaneously record spectra from two volumes of interest. This new technique is called Hadamard-encoded dual-voxel SPECIAL (HD-SPECIAL)., Methods: The SPECIAL sequence consists of a spin echo localized to a column of tissue, preceded by a slice-selective inversion pulse in alternating scans to invert a section of the column. Full localization is achieved by subtraction of the inversion-on scans from the inversion-off scans. In HD-SPECIAL, the two-step inversion scheme is replaced by a four-step Hadamard-encoded scheme involving single-band and dual-band inversion pulses to select two regions of the spin-echo column. By appropriate Hadamard combination of the four acquired shots, spectra can be reconstructed from both desired regions. This approach does not rely on parallel imaging reconstruction. Using a 3T scanner, HD-SPECIAL localization is demonstrated both in phantoms and in the human brain in vivo, and the performance of HD-SPECIAL is assessed by comparing with the conventional SPECIAL sequence., Results: Phantom and in vivo measurements show excellent agreement between measures from HD-SPECIAL and SPECIAL sequences. Relative to consecutive SPECIAL measurements from two regions, HD-SPECIAL reduces the total scan time 2-fold with minimal penalty in terms of spectral quality or SNR., Conclusion: The HD-SPECIAL sequence enables reliable acquisition of MR spectra simultaneously from two regions at 3 T, offering the potential to study interregional variations in metabolite concentrations., (© 2021 International Society for Magnetic Resonance in Medicine.)

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is one of the most frequently used models in aging research. Despite frequency of use, characterization of agerelated neuroanatomical change has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in vivo in a mixed-sexcohort of F344 rats. We identified the greatest vulnerability to aging within the cortex, caudoputamen, hindbrain, and internal capsule, while the influence of sex was strongest in the caudoputamen, hippocampus, nucleus accumbens, and thalamus, many of which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B 0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites., Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC)., Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI., Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed., Competing Interests: Declaration of Competing Interest Jack J. Miller would like to acknowledge the support of a Novo Nordisk Research Fellowship run in conjunction with the University of Oxford. Francisco Reyes-Madrigal has served as a speaker for Janssen (Johnson & Johnson) and AstraZeneca. Marc Thioux and Pim van Dijk were supported by The Netherlands Organization for Health Research and Development (ZonMW) and the Dorhout Mees Foundation. All other authors have no conflict of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices ("Prisma Upgrade protocol") and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence ("vNav protocol"). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1 H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement., Competing Interests: Declaration of Competing Interest Authors report no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Normal aging is associated with numerous biological changes, including altered brain metabolism and tissue chemistry. In vivo characterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful noninvasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields; parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile. The present study reports, for the first time, the simultaneous absolute quantification of brain metabolites and individual macromolecules in aging male and female Fischer 344 rats, measured longitudinally using proton magnetic resonance spectroscopy at 7 T. We identified age- and sex-related changes in neurochemistry, with prominent differences in metabolites implicated in anaerobic energy metabolism, antioxidant defenses, and neuroprotection, as well as numerous macromolecule changes. These findings contribute to our understanding of the neurobiological processes associated with healthy aging, critical for the proper identification and management of pathologic aging trajectories. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect athttps://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: In 2004, Boumezbeur et al proposed a simple yet powerful approach to detect the metabolism of 13 C-enriched substrates in the brain. Their approach consisted of dynamic 1 H-MRS, without a 13 C radiofrequency (RF) channel, and its successful application was demonstrated in monkeys. Since then, this promising method has yet to be applied rigorously in humans. In this study, we revisit the use of dynamic 1 H-MRS to measure the metabolism of 13 C-enriched substrates and demonstrate its application in the human brain., Methods: In healthy participants, 1 H-MRS data were acquired dynamically before and following a bolus infusion of [1- 13 C] glucose. Data were acquired on a 3T clinical MRI scanner using a short-TE SPECIAL sequence, with regions of interest in both anterior and posterior cingulate cortex. Using simulated basis spectra to model signal changes in both 12 C-bonded and 13 C-coupled resonances, the acquired spectra were fit in LCModel to obtain labeling time courses for glutmate and glutamine at both C4 and C3 positions., Results: Presence of the 13 C label was clearly detectable, owing to the pronounced effect of heteronuclear ( 13 C- 1 H) scalar coupling on the observed 1 H spectra. A decrease in signal from 12 C-bonded protons and an increase in signal from 13 C-coupled protons were observed. The fractional enrichment of Glu-C4, (Glu+Gln)-C4, and (Glu+Gln)-C3 at 30 minutes following infusion of [1- 13 C] glucose was similar in both regions: 11% to 13%, 9% to 12% and 3% to 5%, respectively., Conclusion: These preliminary results confirm the feasibility of the use of dynamic 1 H-MRS to monitor 13 C labeling in the human brain, without a 13 C RF channel., (© 2020 International Society for Magnetic Resonance in Medicine.)

This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 μm isotropic image volume composed of 256 coronal slices with 71 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats. Slices in the average brain image were then manually segmented, individually and bilaterally, on the basis of image contrast in conjunction with Paxinos and Watson's (2007) stereotaxic rat brain atlas. Summary statistics (mean and standard deviation of regional volumes) are reported for each brain region across the sample used to generate the atlas, and a statistical comparison of a chosen subset of regional brain volumes between male and female rats is presented. On average, the coefficient of variation of regional brain volumes across all rats in our sample was 4%, with no individual brain region having a coefficient of variation greater than 13%. A full description of methods used, as well as the atlas, the template that the atlas was derived from, and a masking file, can be found on Zenodo at www.zenodo.org/record/3700210. To our knowledge, this is the first MRI atlas created using Fischer 344 rats and will thus provide an appropriate neuroanatomical model for researchers working with this strain.

The glutamate hypothesis of schizophrenia posits aberrant glutamatergic activity in patients with schizophrenia. Levels of glutamate and glutamine can be detected and quantified in vivo by proton magnetic resonance spectroscopy. A related technique, proton magnetic resonance spectroscopic imaging ( 1 H-MRSI), is particularly useful as it simultaneously collects multiple spectra, across multiple voxels, from a single acquisition. The primary aim of this study was to review and discuss the use of 1 H-MRSI to measure levels of glutamate and glutamine in patients with schizophrenia. Additionally, the advantages and disadvantages of using 1 H-MRSI to examine schizophrenia pathophysiology are discussed. A literature search was conducted through Ovid. English language studies utilizing 1 H-MRSI to measure glutamate and glutamine in patients with schizophrenia were identified. Six studies met the inclusion criteria. The included studies provide inconclusive support for glutamatergic elevations within frontal brain regions in patients with schizophrenia. The key benefit of employing 1 H-MRSI to examine schizophrenia pathophysiology appears to be its broader spatial coverage. Future 1 H-MRSI studies utilizing large sample sizes and longitudinal study designs are necessitated to further our understanding of glutamatergic alterations in patients with schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Spectral editing allows direct measurement of low-concentration metabolites, such as GABA, glutathione (GSH) and lactate (Lac), relevant for understanding brain (patho)physiology. The most widely used spectral editing technique is MEGA-PRESS, which has been diversely implemented across research sites and vendors, resulting in variations in the final resolved edited signal. In this paper, we describe an effort to develop a new universal MEGA-PRESS sequence with HERMES functionality for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and timings. New RF pulses were generated for the universal sequence. Phantom experiments were conducted on Philips, Siemens, GE and Canon 3 T MRI scanners using 32-channel head coils. In vivo experiments were performed on the same six subjects on Philips and Siemens scanners, and on two additional subjects, one on GE and one on Canon scanners. On each platform, edited MRS experiments were conducted with the vendor-native and universal MEGA-PRESS sequences for GABA (TE = 68 ms) and Lac editing (TE = 140 ms). Additionally, HERMES for GABA and GSH was performed using the universal sequence at TE = 80 ms. The universal sequence improves inter-vendor similarity of GABA-edited and Lac-edited MEGA-PRESS spectra. The universal HERMES sequence yields both GABA- and GSH-edited spectra with negligible levels of crosstalk on all four platforms, and with strong agreement among vendors for both edited spectra. In vivo GABA+/Cr, Lac/Cr and GSH/Cr ratios showed relatively low variation between scanners using the universal sequence. In conclusion, phantom and in vivo experiments demonstrate successful implementation of the universal sequence across all four major vendors, allowing editing of several metabolites across a range of TEs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: In vivo magnetic resonance spectroscopy (MRS) is the only technique capable of non-invasively assessing metabolite concentrations in the brain. The lack of alternative methods makes validation of MRS measures challenging. The aim of this study is to assess the validity of MRS measures of human brain metabolite concentrations by comparing multiple MRS measures acquired using different MRS acquisition sequences., Methods: Single-voxel SPECIAL and MEGA-PRESS MR spectra were acquired from both the dorsolateral prefrontal cortex and primary motor cortices in 15 healthy subjects. The SPECIAL spectrum, as well as both the edit-off and difference spectra of MEGA-PRESS were each analyzed in LCModel to obtain estimates of the absolute concentrations of total choline (TCh; glycerophosphocholine + phosphocholine), total creatine (TCr; creatine + phosphocreatine), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), NAA + NAAG, glutamate (Glu), glutamine (Gln), Glu + Gln, scyllo-inositol (Scyllo), myo-inositol (Ins), glutathione (GSH), γ-aminobutyric acid (GABA), lactate (Lac) and aspartate (Asp). Then, having obtained up to three independent measures of each metabolite per brain region per subject, correlations between the different measures were assessed., Results: The degree of correlation between measures varied greatly across both the metabolites and sequences tested. As expected, metabolites with the most prominent spectral peaks (TCh, TCr, NAA + NAAG, Ins and Glu) had the most well-correlated measures between methods, while metabolites with less prominent spectral peaks (Lac, Gln, GABA, Asp, and NAAG) tended to have poorly-correlated measures between methods. Some metabolites with relatively less prominent spectral peaks (GSH, Scyllo) had fairly well-correlated measures between some methods. Combining metabolites improved the agreement between methods for measures of NAA + NAAG, but not for Glu + Gln., Conclusions: Given that the ground truth for in vivo MRS measures is never known, the method proposed here provides a promising means to assess the validity of in vivo MRS measures, which has not yet been explored widely., (© 2019 John Wiley & Sons, Ltd.)

Background: Cerebral glutathione (GSH), a marker of oxidative stress, has been quantified in neurodegenerative diseases and psychiatric disorders using proton magnetic resonance spectroscopy (MRS). Using a reproducible MRS technique is important, as it minimizes the impact of measurement technique variability on the study results and ensures that other studies can replicate the results., Hypothesis: We hypothesized that very short echo time (TE) acquisitions would have comparable reproducibility to a long TE MEGA-PRESS acquisition, and that the short TE PRESS acquisition would have the poorest reproducibility., Study Type: Prospective., Subjects/phantoms: Ten healthy adults were scanned during two visits, and six metabolite phantoms containing varying concentrations of GSH and metabolites with resonances that overlap with GSH were scanned once., Field Strength/sequence: At 3T we acquired MRS data using four different sequences: PRESS, SPECIAL, PR-STEAM, and MEGA-PRESS., Assessment: Reproducibility of each MRS sequence across two visits was assessed., Statistical Tests: Mean coefficients of variation (CV) and mean absolute difference (AD) were used to assess reproducibility. Linear regressions were performed on data collected from phantoms to examine the agreement between known and quantified levels of GSH., Results: Of the four techniques, PR-STEAM had the lowest mean CV and AD (5.4% and 7.5%, respectively), implying excellent reproducibility, followed closely by PRESS (5.8% and 8.2%) and SPECIAL (8.0 and 10.1%), and finally by MEGA-PRESS (13.5% and 17.1%). Phantom data revealed excellent fits (R 2 ≥ 0.98 or higher) using all methods., Data Conclusion: Our data suggest that GSH can be quantified reproducibly without the use of spectral editing., Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:176-183., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Indirect 13 C MRS by proton-observed carbon editing (POCE) is a powerful method to study brain metabolism. The sensitivity of POCE-MRS can be enhanced through the use of short TEs, which primarily minimizes homonuclear J-evolution related losses; previous POCE-MRS implementations use longer than optimal echo times due to sequence limitations, or short TE image selected in vivo spectroscopy-based multi-shot acquisitions for 3D localization. To that end, this paper presents a novel single-shot point resolved spectroscopy (PRESS)-localized POCE-MRS sequence that involves the application of simultaneous editing and localization pulses (SEAL)-PRESS, allowing the TE to be reduced to a theoretically optimal value of ∼ 1/J HC ., Methods: The optimized SEAL-PRESS sequence was first evaluated in simulation and in phantom; next, the sequence was validated with dynamic in vivo POCE-MRS performed in a rat preparation during a 1,6- 13 C 2 -Glc infusion, and on a microwave fixed rat brain following a 2-hour [1,6- 13 C 2 ]-Glc infusion. POCE spectra from the SEAL-PRESS sequence were compared against a previously described 12.6-ms PRESS-POCE sequence utilizing a classical carbon editing scheme., Results: The SEAL-PRESS sequence provides > 95% editing efficiency, optimal sensitivity, and localization for POCE MRS with an overall sequence TE of 8.1 ms. Signal amplitude of 13 C-labeled metabolites Glu-H4, Gln-H4, Glx-H3, Glc-H6 +Glx-H2, and Asp-H2 were shown to be improved by >17% relative to a 12.6-ms PRESS-POCE sequence in vivo., Conclusion: We report for the first time, a single-shot PRESS-localized and edited 8.1-ms TE POCE-MRS sequence with optimal sensitivity, editing efficiency, and localization., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: Detection of endogenous metabolites using multiplexed editing substantially improves the efficiency of edited magnetic resonance spectroscopy. Multiplexed editing (i.e., performing more than one edited experiment in a single acquisition) requires a tailored, robust approach for correction of frequency and phase offsets. Here, a novel method for frequency and phase correction (FPC) based on spectral registration is presented and compared against previously presented approaches., Methods: One simulated dataset and 40 γ-aminobutyric acid-/glutathione-edited HERMES datasets acquired in vivo at three imaging centers were used to test four FPC approaches: no correction; spectral registration; spectral registration with post hoc choline-creatine alignment; and multistep FPC. The performance of each routine for the simulated dataset was assessed by comparing the estimated frequency/phase offsets against the known values, whereas the performance for the in vivo data was assessed quantitatively by calculation of an alignment quality metric based on choline subtraction artifacts., Results: The multistep FPC approach returned corrections that were closest to the true values for the simulated dataset. Alignment quality scores were on average worst for no correction, and best for multistep FPC in both the γ-aminobutyric acid- and glutathione-edited spectra in the in vivo data., Conclusions: Multistep FPC results in improved correction of frequency/phase errors in multiplexed γ-aminobutyric acid-/glutathione-edited magnetic resonance spectroscopy experiments. The optimal FPC strategy is experiment-specific, and may even be dataset-specific. Magn Reson Med 80:21-28, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: In vivo carbon-13 ( 13 C) MR spectroscopy (MRS) is capable of measuring energy metabolism and neuroenergetics, noninvasively in the brain. Indirect ( 1 H-[ 13 C]) MRS provides sensitivity benefits compared with direct 13 C methods, and normally includes a 1 H surface coil for both localization and signal reception. The aim was to develop a coil platform with homogenous B1+ and use short conventional pulses for short echo time proton observed carbon edited (POCE) MRS., Methods: A 1 H-[ 13 C] MRS coil platform was designed with a volumetric resonator for 1 H transmit, and surface coils for 1 H reception and 13 C transmission. The Rx-only 1 H surface coil nullifies the requirement for a T/R switch before the 1 H preamplifier; the highpass filter and preamplifier can be placed proximal to the coil, thus minimizing sensitivity losses inherent with POCE-MRS systems described in the literature. The coil platform was evaluated with a PRESS-POCE sequence (TE = 12.6 ms) on a rat model., Results: The coil provided excellent localization, uniform spin nutation, and sensitivity. 13 C labeling of Glu-H4 and Glx-H3 peaks, and the Glx-H2 peaks were observed approximately 13 and 21 min following the infusion of 1- 13 C glucose, respectively., Conclusion: A convenient and sensitive platform to study energy metabolism and neurotransmitter cycling is presented. Magn Reson Med 79:628-635, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: We describe the fabrication and performance of a chronic in situ coil system designed to allow focal brain stimulation in rats while acquiring functional MRI data., New Method: An implantable receive-only surface radiofrequency coil (iCoil) was designed to be fitted subcutaneously, directly onto to the rat skull surface during the intracerebral cannulation procedure. The coil is fixed in place using acrylic dental cement anchored to four screws threaded into the skull. To demonstrate the use of this coil system in situ, whole-brain functional MRI scans were acquired during various stimuli, including intracranial microinfusions of bicuculline and morphine in the prefrontal cortex and ventral tegmental area, respectively., Results/comparison to Other Methods: SNR performance of the iCoil was superior to three commercially-available coils, in some instances by a factor of two. Widespread BOLD activation was observed in response to bicuculline and morphine microinfusions., Conclusion: A new approach was demonstrated for high-SNR MR imaging of the brain in rats with intracranial implants using an implantable surface coil. This approach enables mapping the functional response to highly targeted stimuli such as intracranial microinfusions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To investigate the quantitative impact of frequency drift on Gamma-Aminobutyric acid (GABA+)-edited MRS of the human brain at 3 Tesla (T)., Methods: Three sequential GABA+-edited MEGA-PRESS acquisitions were acquired in fifteen sessions; in ten of these, MRS was preceded by functional MRI (fMRI) to induce frequency drift, which was estimated from the creatine resonance at 3.0 ppm. Simulations were performed to examine the effects of frequency drift on the editing efficiency of GABA and co-edited macromolecules (MM) and of subtraction artifacts on GABA+ quantification. The efficacy of postprocessing frequency correction was also investigated., Results: Gradient-induced frequency drifts affect GABA+ quantification for at least 30 min after imaging. Average frequency drift was low in control sessions and as high as -2 Hz/min after fMRI. Uncorrected frequency drift has an approximately linear effect on GABA+ measurements with a -10 Hz drift resulting in a 16% decrease in GABA+, primarily due to subtraction artifacts., Conclusion: Imaging acquisitions with high gradient duty cycles can impact subsequent GABA+ measurements. Postprocessing can address subtraction artifacts, but not changes in editing efficiency or GABA:MM signal ratios; therefore, protocol design should avoid intensive gradient sequences before edited MRS Magn Reson Med 72:941-948, 2014. © 2013 Wiley Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

PurposeHeating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.MethodA standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).ResultsOf the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.DiscussionThis study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

Recent findings suggest that cortical gamma aminobutyric acid (GABA) levels may provide a surrogate marker for a number of psychiatric and neurological conditions, as well as behavioural traits. However, the natural variability of GABA levels in the human brain over long periods of time (>8days) has not yet been studied. The purpose of this work was to investigate the long-term variability of GABA concentrations in the human occipital cortex. Nineteen healthy male participants were recruited and underwent two sessions of magnetic resonance spectroscopy (MRS) to determine occipital GABA levels with an average between-session interval of 7months. We assessed between-session variability, as well as the correlation between session 1 and session 2 GABA measurements. The mean coefficient of variation between sessions was 4.3% (bootstrap 95% confidence interval: 2.5, 6.4), which is comparable to reported GABA variability measurements over much shorter time intervals (<8days). A significant positive correlation was observed between session 1 and session 2 GABA measurements (r=0.53, p=0.014), and the intra-class correlation coefficient was calculated to be 0.52 which was also statistically significant (p=0.012). These findings establish experimentally that GABA concentrations in the occipital cortex, as measured by MRS, are relatively stable over periods as long as 7months. The findings have significant implications for the internal validity of longitudinal studies of GABA levels in the human brain, and they lend foundational support to studies relating GABA levels to behavioural traits in healthy individuals. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy ( 1 H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E ( APOE ) ε4, an established risk gene for AD. We quantified metabolites within an 8 cm 3 voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20–40 years) and 151 cognitively healthy older individuals (60–85 years). All 1 H-MRS scans were performed at 3 T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in 1 H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample. [ABSTRACT FROM AUTHOR]

Fragile-X syndrome (FXS) and Neurofibromatosis of type 1 (NF-1) are two monogenic disorders sharing neurobehavioral symptoms and pathophysiological mechanisms. Namely, preclinical models of both conditions show overactivity of the mTOR signaling pathway as well as GABAergic alterations. However, despite its potential clinical relevance for these disorders, the GABAergic system has not been systematically studied in humans. In the present study, we used an extensive transcranial magnetic stimulation (TMS) assessment battery in combination with magnetic resonance spectroscopy (MRS) to provide a comprehensive picture of the main inhibitory neurotransmitter system in patients with FXS and NF1. Forty-three participants took part in the TMS session (15 FXS, 10 NF1, 18 controls) and 36 in the MRS session (11 FXS, 14 NF1, 11 controls). Results show that, in comparison to healthy control participants, individuals with FXS and NF1 display lower GABA concentration levels as measured with MRS. TMS result show that FXS patients present increased GABA B -mediated inhibition compared to controls and NF1 patients, and that GABA A -mediated intracortical inhibition was associated with increased excitability specifically in the FXS groups. In line with previous reports, correlational analyses between MRS and TMS measures did not show significant relationships between GABA-related metrics, but several TMS measures correlated with glutamate+glutamine (Glx) levels assessed with MRS. Overall, these results suggest a partial overlap in neurophysiological alterations involving the GABA system in NF1 and FXS, and support the hypothesis that MRS and TMS assess different aspects of the neurotransmitter systems. • We used TMS and MRS to investigate GABA function in patients with NF1 and FXS. • NF1 and FXS patients show reduced GABA concentration levels. • Several TMS measures correlate with Glx levels assessed with MRS. • There is a partial overlap in GABA alterations in NF1 and FXS. [ABSTRACT FROM AUTHOR]