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Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study., Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T 2 correction based on the dual-TE water integrals were compared with: 1) T 2 correction based on the default white matter and gray matter T 2 reference values in Osprey and 2) shorter WM and GM T 2 values from recent literature., Results: No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T 2 correction based on shorter T 2 values showed better agreement to the dual-TE water integral ratio., Conclusions: ISTHMUS facilitated data acquisition and post-processing and reduced operator workload to eliminate potential human error., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD)., Methods: Nine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T 1 H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling., Results: Baseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms., Limitations: Sample size., Conclusions: These preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response., (Copyright © 2020. Published by Elsevier B.V.)

Background: Processing and quantitative analysis of magnetic resonance spectroscopy (MRS) data are far from standardized and require interfacing with third-party software. Here, we present Osprey, a fully integrated open-source data analysis pipeline for MRS data, with seamless integration of pre-processing, linear-combination modelling, quantification, and data visualization., New Method: Osprey loads multiple common MRS data formats, performs phased-array coil combination, frequency-and phase-correction of individual transients, signal averaging and Fourier transformation. Linear combination modelling of the processed spectrum is carried out using simulated basis sets and a spline baseline. The MRS voxel is coregistered to an anatomical image, which is segmented for tissue correction and quantification is performed based upon modelling parameters and tissue segmentation. The results of each analysis step are visualized in the Osprey GUI. The analysis pipeline is demonstrated in 12 PRESS, 11 MEGA-PRESS, and 8 HERMES datasets acquired in healthy subjects., Results: Osprey successfully loads, processes, models, and quantifies MRS data acquired with a variety of conventional and spectral editing techniques., Comparison With Existing Method(s): Osprey is the first MRS software to combine uniform pre-processing, linear-combination modelling, tissue correction and quantification into a coherent ecosystem. Compared to existing compiled, often closed-source modelling software, Osprey's open-source code philosophy allows researchers to integrate state-of-the-art data processing and modelling routines, and potentially converge towards standardization of analysis., Conclusions: Osprey combines robust, peer-reviewed data processing methods into a modular workflow that is easily augmented by community developers, allowing the rapid implementation of new methods., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The role of testosterone (T) in the pathophysiology of affective disorders and anxiety is broadly supported. Evidence suggests that T has anxiolytic and antidepressant properties. One proposed route for the central effects of T is its interaction with the gamma-aminobutyric acid (GABA) system. We explored the relationship between T levels and GABA+ levels in anterior-cingulate (ACC) and the posterior-cingulate (PCC) regions in depressed women, using magnetic resonance spectroscopy ( 1 H-MRS)., Methods: Twenty-one depressed patients with regularly cycling who were not taking hormonal or psychotropic drugs were recruited. We assessed severity of depression using the Hamilton Depression Rating Scale (HDRS). Blood samples were taken for quantification of free (FT) and total testosterone (TT) on the day of the magnetic resonance (MR) scan. We evaluated GABA+ levels in the PCC and ACC, using the Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence. Pearson correlations were used to evaluate the association between FT, TT, GABA+ concentrations, and HDRS scores., Results: TT and FT levels were positively correlated with GABA+ levels in the PCC. No correlation was observed between T levels and GABA+ levels in the ACC. The HDRS total scores correlated negatively with FT levels., Limitations: Limitations include the cross-sectional evaluation and the lack of a comparative healthy group., Conclusions: Our findings suggest that the potential anxiolytic and antidepressant properties of T are related to increased GABA+ levels in the PCC. This observation may contribute to increased understanding of the role of T in depressive and anxiety symptoms in women., (Copyright © 2018. Published by Elsevier B.V.)

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is known to be fundamental to the neuronal processes underlying visual orientation and vibrotactile frequency and amplitude discrimination. Previous studies have demonstrated that performance on visual and vibrotactile psychophysics tasks is associated with in vivo measurements of "GABA+" levels - a measure of GABA substantially contaminated by a macromolecular (MM) signal. Here, we establish that these prior findings are indeed driven by the GABA fraction of that signal. Edited magnetic resonance spectroscopy (MRS) was used to measure GABA with and without MM suppression in the sensorimotor (SM1) and occipital cortices in 14 healthy male adults. Volunteers also underwent psychophysical experiments to assess their performance on visual orientation discrimination and vibrotactile amplitude and frequency discrimination. We show that MM-suppressed GABA levels correlate more strongly with individual differences in vibrotactile (in the case of SM1 GABA; amplitude: r = -0.63, p = 0.03; frequency: r = -0.62, p = 0.02) and visual orientation (in the case of occipital GABA; r = -0.59, p = 0.05) discrimination thresholds than GABA levels contaminated by MM (vibrotactile amplitude: r = -0.36, p = 0.30; vibrotactile frequency: r = -0.53, p = 0.09; visual orientation: r = 0.21, p = 0.55). These findings further support the view that measurements of endogenous GABA acquired with edited MRS can usefully probe neurochemical-behavioral relationships in humans. Moreover, the more specific measurement of GABA used in this study provides increased statistical power to observe these regionally specific relationships., (Copyright © 2018. Published by Elsevier B.V.)

Background: The relationships between scan duration, signal-to-noise ratio (SNR) and sample size must be considered and understood to design optimal GABA-edited magnetic resonance spectroscopy (MRS) studies., New Method: Simulations investigated the effects of signal averaging on SNR, measurement error and group-level variance against a known ground truth. Relative root mean square errors (measurement error) and coefficients of variation (group-level variance) were calculated. GABA-edited data from 18 participants acquired from five voxels were used to examine the relationships between scan duration, SNR and quantitative outcomes in vivo. These relationships were then used to determine the sample sizes required to observe different effect sizes., Results: In both simulated and in vivo data, SNR increased with the square root of the number of averages. Both measurement error and group-level variance were shown to follow an inverse-square-root function, indicating no significant impact of cumulative artifacts. Comparisons between the first two-thirds of the data and the full dataset showed no statistical difference in group-level variance. There was, however, some variability across the five voxels depending on SNR, which impacted the sample sizes needed to detect group differences in specific brain regions., Comparison With Existing Methods: Typical scan durations can be reduced if taking into account a statistically acceptable amount of variance and the magnitudes of predicted effects., Conclusions: While scan duration in GABA-edited MRS has typically been considered in terms of SNR, it is more appropriate to think in terms of the amount of measurement error and group-level variance that provides sufficient statistical power., (Copyright © 2018 Elsevier B.V. All rights reserved.)