Reproducibility and effect of tissue composition on cerebellar γ-aminobutyric acid (GABA) MRS in an elderly population

Long, Zaiyang; Dyke, Jonathan P.; Ma, Ruimin; Huang, Chaorui; Louis, Elan D.; Dydak, Ulrike

doi:10.1002/nbm.3381

Cited by 22 publications

(22 citation statements)

References 70 publications

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“…The whole-dataset CV reported in this study falls well within the range of inter-individual CVs observed for edited GABA+ measurements in the literature: 6–24% (Bogner et al, 2010; Evans et al, 2010; Geramita et al, 2011; Long et al, 2015; Mikkelsen et al, 2016a; O’Gorman et al, 2011). That a majority of the total variance in the data was participant-level variance indicates that initial steps taken to standardize acquisition parameters across vendors (most notably TR, TE and editing pulse bandwidth) were largely successful.…”

Section: Discussionsupporting

confidence: 87%

Big GABA: Edited MR spectroscopy at 24 research sites

et al. 2017

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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.

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Section: Discussionsupporting

confidence: 87%

Big GABA: Edited MR spectroscopy at 24 research sites

et al. 2017

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“…Most previous studies evaluated the MEGA‐PRESS sequence for quantification of GABA, Glu, Gln, and Glx or GABA only . Two studies quantified Glx by JPRESS .…”

Section: Discussionmentioning

confidence: 99%

“…Most previous studies evaluated the MEGA-PRESS sequence for quantification of GABA, Glu, Gln, and Glx or GABA only. [10][11][12][13][14][15][16][17][18] Two studies quantified Glx by JPRESS. 36,37 CV evaluation for test-retest reliability has been applied extensively to all sequences in several investigations, as for MEGA-PRESS 16 and JPRESS.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the previously published studies investigating the reliability of MRS methods have focused on characterizing the test–retest reproducibility of GABA concentrations derived with MEGA‐PRESS . Almost all previous works reported coefficient of variation (CV) values only, and few studies compared intraclass correlation coefficients (ICC), using mainly the MEGA‐PRESS sequence.…”

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confidence: 99%

“…8,9 Most of the previously published studies investigating the reliability of MRS methods have focused on characterizing the test-retest reproducibility of GABA concentrations derived with MEGA-PRESS. [10][11][12][13][14][15][16][17][18] Almost all previous works reported coefficient of variation (CV) values only, and few studies compared intraclass correlation coefficients (ICC), 15,[17][18][19] using mainly the MEGA-PRESS sequence. Three papers 15,17,19 discussed Pearson's correlations and only van Veenendaal et al 10 reported Bland-Altman (BA) plots.…”

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confidence: 99%

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Test–Retest Reliability of the Brain Metabolites GABA and Glx With JPRESS, PRESS, and MEGA‐PRESS MRS Sequences in vivo at 3T

Baeshen

Wyss

Henning

et al. 2019

Magnetic Resonance Imaging

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Background The optimization of magnetic resonance spectroscopy (MRS) sequences allows improved diagnosis and prognosis of neurological and psychological disorders. Thus, to assess the test–retest and intersequence reliability of such MRS sequences in quantifying metabolite concentrations is of clinical relevance. Purpose To evaluate the test–retest and intersequence reliability of three MRS sequences to estimate GABA and Glx = Glutamine+Glutamate concentrations in the human brain. Study Type Prospective. Subjects Eighteen healthy participants were scanned twice (range: 1 day to 1 week between the two sessions) with identical protocols. Field Strength/Sequence 3T using a 32‐channel SENSE head coil in the PCC region; PRESS, JPRESS, and MEGA‐PRESS sequences. Assessment Metabolite concentrations were estimated using LCModel (for PRESS and MEGA‐PRESS) and ProFit2 (for JPRESS). Statistical Tests The test–retest reliability was evaluated by Wilcoxon signed‐rank tests, Pearson's r correlation coefficients, intraclass‐correlation coefficients (ICC), coefficients of variation (CV), and by Bland–Altman (BA) plots. The intersequence reliability was assessed with Wilcoxon signed‐rank tests, Pearson's r correlation coefficients, and BA plots. Results For GABA, only the MEGA‐PRESS sequence showed a moderate test–retest correlation (r = 0.54, ICC = 0.5, CV = 8.8%) and the BA plots indicated good agreement (P > 0.05) for all sequences. JPRESS provided less precise results and PRESS was insensitive to GABA. For Glx, the r and ICC values for PRESS (r = 0.87, ICC = 0.9, CV = 2.9%) and MEGA‐PRESS (r = 0.70, ICC = 0.7, CV = 5.3%) reflect higher correlations, compared with JPRESS (r = 0.39, ICC = 0.4, CV = 20.1%). Data Conclusion MEGA‐PRESS and JPRESS are suitable for the reliable detection of GABA, the first being more precise. The three sequences included in the study can measure Glx concentrations. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1181–1191.

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Age‐related differences in GABA levels are driven by bulk tissue changes

Maes

Hermans

Pauwels

et al. 2018

Human Brain Mapping

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Levels of GABA, the main inhibitory neurotransmitter in the brain, can be regionally quantified using magnetic resonance spectroscopy (MRS). Although GABA is crucial for efficient neuronal functioning, little is known about age-related differences in GABA levels and their relationship with age-related changes in brain structure. Here, we investigated the effect of age on GABA levels within the left sensorimotor cortex and the occipital cortex in a sample of 85 young and 85 older adults using the MEGA-PRESS sequence. Because the distribution of GABA varies across different brain tissues, various correction methods are available to account for this variation. Considering that these correction methods are highly dependent on the tissue composition of the voxel of interest, we examined differences in voxel composition between age groups and the impact of these various correction methods on the identification of age-related differences in GABA levels. Results indicated that, within both voxels of interest, older (as compared to young adults) exhibited smaller gray matter fraction accompanied by larger fraction of cerebrospinal fluid. Whereas uncorrected GABA levels were significantly lower in older as compared to young adults, this age effect was absent when GABA levels were corrected for voxel composition. These results suggest that age-related differences in GABA levels are at least partly driven by the age-related gray matter loss. However, as alterations in GABA levels might be region-specific, further research should clarify to what extent gray matter changes may account for age-related differences in GABA levels within other brain regions.

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Reproducibility and effect of tissue composition on cerebellar γ-aminobutyric acid (GABA) MRS in an elderly population

Cited by 22 publications

References 70 publications

Big GABA: Edited MR spectroscopy at 24 research sites

Big GABA: Edited MR spectroscopy at 24 research sites

Test–Retest Reliability of the Brain Metabolites GABA and Glx With JPRESS, PRESS, and MEGA‐PRESS MRS Sequences in vivo at 3T

Age‐related differences in GABA levels are driven by bulk tissue changes

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