Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study’s protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.
Accurate and reliable quantification of brain metabolites measured in vivo using 1 H magnetic resonance spectroscopy (MRS) is a topic of continued interest in the field. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, we analyze spectrally edited -aminobutyric acid (GABA) MRS data and quantify GABA levels relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using standard GABA+ editing. Unsuppressed water acquisitions from the same volume of interest were acquired for signal referencing. Whole-brain T1-weighted structural images were acquired and tissue-segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA+ measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17%, which was largely driven by vendor-related differences according to a linear mixed-effects analysis. The mean within-site coefficient of variation was 9%. Vendor differences contributed 53% to the total variance in the data, while the remaining variance was attributed to site-(11%) and participant-level (36%) effects. Results from an exploratory analysis suggested that the vendor differences were related to the water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA+ measurements exhibit levels of variance similar to creatine-referenced GABA+ measurements. It is concluded that quantification using internal tissue water referencing remains a viable and reliable method for the in vivo quantification of GABA+ levels.
Background:The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels.Purpose: To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods:An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted P boot ). Results:In total, 296 participants (mean age, 26 years 6 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (P boot . .90), N-acetylaspartate and N-acetylaspartylglutamate (P boot = .13), or glutamate and glutamine (P boot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (P boot = .08), aspartate (P boot . .90), glutathione (P boot . .90), or lactate (P boot = .28). Conclusion:Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the siterelated effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols.
In his recent report, Lord Adebowale (2013) described mental health issues as "core police business". The recent retrenchment in mental health and wider public services mean that the demands on the police in this area are likely to increase. Mental health triage is a concept that has been adapted from general and mental health nursing for use in a policing context. The overall aim of triage is to ensure more effective health outcomes and the more effective use of resources. This article examines the current policy and practice in this area. It then goes on to explore the models of mental health triage that have been developed to try and improve working between mental health services and the police.
Manganese (Mn) is an essential trace metal. It is also a component of welding fume. Chronic inhalation of manganese from welding fume has been associated with decreased neurological function. Currently, there is not a universally recognized biomarker for Mn exposure; however, hair and toenails have shown promise. In a cohort of 45 male welders and 35 age-matched factory control subjects, we assessed the sensitivity and specificity of toenail Mn to distinguish occupationally exposed subjects from unexposed controls. Further we examined the exposure time window that best correlates with the proposed biomarker, and investigated if non-occupational exposure factors impacted toenail Mn concentrations. Toenail clippings were analyzed for Mn using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Exposure to respirable Mn-containing particles (<4 µm) was estimated using an exposure model that combines personal air monitoring, work history information, and dietary intake to estimate an individual's exposure to Mn from inhalation of welding fume. We assessed the group differences in toenail concentrations using a Student's t-test between welders and control subjects and performed a receiver operating characteristic (ROC) curve analysis to identify a threshold in toenail concentration that has the highest sensitivity and specificity in distinguishing welders from control subjects. Additionally, we performed mixed-model regressions to investigate the association between different exposure windows and toenail Mn concentrations. We observed that toenail Mn concentrations were significantly elevated among welders compared to control subjects (6.87 ± 2.56 versus 2.70 ± 1.70 µg g −1 ; P < 0.001). Our results show that using a toenail Mn concentration of 4.14 µg g −1 as cutoff allows for discriminating between controls and welders with 91% specificity and 94% sensitivity [area under curve (AUC) = 0.98]. Additionally, we found that a threshold of 4.66 µg g −1 toenail Mn concentration enables a 90% sensitive and 90% specific discrimination (AUC = 0.96) between subjects with average exposure above or below the American Conference of Governmental dow of 7-12 months prior to the nail being clipped. Investigating which exposure window was best reflected by toenail Mn reproduced the result from another study of toenail Mn being significantly (P < 0.001) associated with exposure 7-12 months prior to the nail being clipped. Lastly, we found that dietary intake, body mass index, age, smoking status, and ethnicity had no significant effect on toenail Mn concentrations. Our results suggest that toenail Mn is a sensitive, specific, and easy-toacquire biomarker of Mn exposure, which is feasible to be used in an industrial welder population.
Although diagnosed on the basis of deficits in social communication and interaction, autism spectrum disorder (ASD) is also characterized by superior performance on a variety of visuospatial tasks, including visual search. In neurotypical individuals, region‐specific concentrations of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA) are associated with individual differences in attention and perception. While it has been hypothesized that ASD may be associated with an excitatory–inhibitory imbalance, it remains unclear how this may contribute to accelerated visual search performance in individuals with ASD. To investigate this, 21 children with ASD and 20 typically developing children participated in a visual search task and a magnetic resonance spectroscopy study to detect neurochemical concentrations, including GABA. Region‐specific neurochemicals were examined in the right frontal eye fields, right temporal–parietal junction (rTPJ), and bilateral visual cortex (VIS). GABA concentrations did not differ between groups; however, in children with ASD, greater GABA concentration in the VIS was related to more efficient search. Additionally, lower VIS GABA levels were also associated with increased social impairment. Finally, we found reduced N‐acetyl aspartate, total creatine, glutamate and glutamine (Glx), GABA/Glx in the rTPJ, suggestive of neuronal dysfunction in a critical network hub. Our results show that GABA concentrations in the VIS are related to efficient search in ASD, thus providing further evidence of enhanced discrimination in ASD. Autism Res 2020, 13: 550–562. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Children with autism spectrum disorder (ASD) often perform better than their non‐ASD peers on visual search tasks; however, it is unclear how they achieve this superior performance. Using magnetic resonance spectroscopy to measure neurochemicals in the brain, we found that the level of one, gamma‐aminobutyric acid, in the visual cortex was directly related to search abilities in children with ASD. These results suggest that faster search may relate to enhanced perceptual functioning in children with ASD.
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 ...
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