Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

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 Pboot). Results In total, 296 participants (mean age, 26 years ± 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 (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .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 site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. 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, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and 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% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Big GABA: Edited MR spectroscopy at 24 research sites.

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.

Within- and between-session reproducibility of GABA measurements with MR spectroscopy.

PURPOSE: The reproducibility of the MEGA-PRESS (MEshcher-GArwood Point RESolved Spectroscopy) MR spectroscopy sequence for the measurement of gamma- aminobutyric acid (GABA) is addressed, focusing on optimizing the number of repetitions at two voxel locations in the human brain and associated possibilities in analysis tools. MATERIALS AND METHODS: Two 20-min MEGA-PRESS acquisitions were run (echo time = 68 ms, repetition time = 1800 ms, repetitions = 328): one from a 21 mL volume in the anterior cingulate cortex (ACC) and one from a 22 mL volume in the left Broca's area in 21 healthy male volunteers (age 32 years ± 6[SD]). Subjects were scanned twice with identical protocols, 1 week apart. Data were acquired on a 3 Tesla GE Discovery 750 scanner using a 32-channel head coil. Spectroscopy data were partitioned into shorter epochs, numerically equivalent to scans of progressively increasing duration, and compared both within and between sessions. Three different analysis schemes were applied: (1) Vendor prototype preprocessor, with quantification by LCModel. (2) Pure Gannet pipeline. (3) Preprocessing with Gannet, and quantification with LCModel. The coefficient of variation (CV) were calculated as a measure of reproducibility. RESULTS: Increasing the number of repetitions showed improvements for within- and between-session reproducibility up to around 218 repetitions. (CV ranging from 4 to 14%). Gannet combined with LCModel approach proved the best method. (CV = 4-5%). Measurements from the ACC area had higher CVs than the Broca area. (CV = 6-14% versus 4-7%). CONCLUSION: Measurement in the Broca area yields better reproducibility than the ACC. With appropriate acquisition times and preprocessing tools, measurements from the ACC area are also reliable. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:421-430.

MEGA-PRESS and PRESS measure oxidation of glutathione in a phantom.

PURPOSE: Investigate the possibility of measuring changes in glutathione (GSH) concentration using the MRS PRESS and MEGA-PRESS sequences by tracking the natural oxidation of GSH, and to examine the accuracy of the two methods. METHODS: 122 GSH edited MEGA-PRESS and PRESS acquisitions were acquired on a "braino" based phantom +3.0 mM GSH during a period of 11 days. All spectra were analyzed in LCModel. (The MEGA-PRESS data were first preprocessed in Matlab). Degradation curves were modeled. A one year follow-up on the same phantom and measurements from a similar phantom without GSH and one pure GSH phantom were also included. RESULTS: Both MEGA-PRESS and PRESS showed degradation of the measured GSH signal. Modeling the exponential decay of the GSH signal in MEGA-PRESS and PRESS gave for t = 0; 2.9 i.u. for MEGA-PRESS and 2.3 i.u. for PRESS. As t increased, the GSH concentration converged to zero for MEGA-PRESS but not for PRESS (0.7 i.u.). GSH for the one year follow up were 0.0 i.u. for MEGA-PRESS and 0.6 i.u. for PRESS. Similar phantom without GSH yielded 0.0 i.u. for both MEGA-PRESS and PRESS. CONCLUSION: It is possible to measure changes in GSH concentration in a phantom using both PRESS and MEGA-PRESS techniques, however the PRESS spectrum appears to include oxidized GSH (GSSG). In addition, GSH edited MEGA-PRESS measurement gives more precise values at lower GSH concentrations.

The Evans' Index revisited: New cut-off levels for use in radiological assessment of ventricular enlargement in the elderly.

BACKGROUND AND PURPOSE: Assessment of ventricular enlargement is subjective and based on the radiologist's experience. Linear indices, such as the Evans Index (EI), have been proposed as markers of ventricular volume with an EI≥0.3 indicating pathologic ventricular enlargement in any subject. However, normal range for EI measured on magnetic resonance imaging (MRI) scans are lacking in healthy elderly according to age and sex. We propose new age and sex specific cut-off values for ventricular enlargement in the elderly population. MATERIALS AND METHODS: 534 participants (53% women) aged 65-84 years; 226 patients with Alzheimer's disease (AD), and 308 healthy elderly controls (CTR) from the AddNeuroMed and ADNI studies were included. The cut-off for pathological ventricular enlargement was estimated from healthy elderly categorized into age groups of 5 years range and defined as EI 97,5 percentile (mean+2SD). Cut-off values were tested on patients with Alzheimer's disease and a small sample of patients with probable idiopathic normal pressure hydrocephalus (iNPH) to assess the sensitivity. RESULTS: The range of the EI in healthy elderly is wide and 29% of the CTR had an EI of 0.3 or greater. The EI increases with age in both CTR and AD, and the overall EI for women were lower than for men (p<0.001). New EI cut off values for male/female: 65-69 years 0.34/0.32, 70-74 years 0.36/0.33, 75-79 years 0.37/0.34 and 80-84 years 0.37/0.36. When applying the proposed cut-offs for EI in men and women aged 65-84, they differentiated between iNPH and CTR with a sensitivity of 80% and for different age and sex categories of AD and CTR with a sensitivity and specificity of 0-27% and 91-98%, respectively. CONCLUSION: The range of the EI measurements in healthy elderly is wide, and a cut-off value of 0.3 cannot be used to differentiate between normal and enlarged ventricles in individual cases. The proposed EI thresholds from the present study show good sensitivity for the iNPH diagnosis.

"Brain MR spectroscopy in autism spectrum disorder-the GABA excitatory/inhibitory imbalance theory revisited".

Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of γ-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels.