Doubly selective multiple quantum chemical shift imaging and T 1 relaxation time measurement of glutathione (GSH) in the human brain in vivo
The Nathan Kline Institute, Medical Physics, Orangeburg, NY, 10962, USA. .NMR in Biomedicine (Impact Factor: 3.04). 01/2013; 26(1). DOI: 10.1002/nbm.2815
Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly-selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ-Amino butyric acid (GABA) and macromolecules. GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T(1) ) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than that of other metabolites. This GSH-CSI method permits us to address regional differences of GSH in the human brain under conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. Copyright © 2012 John Wiley & Sons, Ltd.
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ABSTRACT: A reduction in key antioxidants such as glutathione has been noted in brain tissue undergoing oxidative stress in aging and neurodegeneration. To date, no dietary factor has been linked to a higher glutathione concentration. However, in an earlier pilot study, we showed evidence of a positive association between cerebral glutathione and dairy intake. We tested the hypothesis that dairy food consumption is associated with cerebral glutathione concentrations in older adults. In this observational study, we measured cerebral glutathione concentrations in 60 healthy subjects (mean ± SD age: 68.7 ± 6.2 y) whose routine dairy intakes varied. Glutathione concentrations were measured by using a unique, noninvasive magnetic resonance chemical shift imaging technique at 3 T and compared with dairy intakes reported in 7-d food records. Glutathione concentrations in the frontal [Spearman's rank-order correlation (rs) = 0.39, P = 0.013], parietal (rs = 0.50, P = 0.001), and frontoparietal regions (rs = 0.47, P = 0.003) were correlated with average daily dairy servings. In particular, glutathione concentrations in all 3 regions were positively correlated with milk servings (P ≤ 0.013), and those in the parietal region were also correlated with cheese servings (P = 0.015) and calcium intake (P = 0.039). Dairy intake was related to sex, fat-free mass, and daily intakes of energy, protein, and carbohydrates. However, when these factors were controlled through a partial correlation, correlations between glutathione concentrations and dairy and milk servings remained significant. Higher cerebral glutathione concentrations were associated with greater dairy consumption in older adults. One possible explanation for this association is that dairy foods may serve as a good source of substrates for glutathione synthesis in the human brain. © 2015 American Society for Nutrition.American Journal of Clinical Nutrition 02/2015; 101(2):287-93. DOI:10.3945/ajcn.114.096701 · 6.77 Impact Factor
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ABSTRACT: Background Extant data from in vivo animal model and postmortem studies indicate that Alzheimer’s disease (AD) pathology is associated with reduction of the brain antioxidant glutathione (GSH), yet direct clinical evidence has been lacking. In this study, we investigated GSH modulation in the brain with AD and assessed the diagnostic potential of GSH estimation in hippocampi (HP) and frontal cortices (FC) as a biomarker for AD and its prodromal stage, mild cognitive impairment (MCI). Methods Brain GSH levels were measured in HP of 21 AD, 22 MCI, and 21 healthy old controls (HC) and FC of 19 AD, 19 MCI, and 28 HC with in vivo proton magnetic resonance spectroscopy (MRS). The association between GSH levels and clinical measures of AD progression was tested. Linear regression models were used to determine the best combination of GSH estimation in these brain regions for discrimination between AD, MCI, and HC. Results AD-dependent reduction of GSH was observed in both HP and FC (p <0.001). Furthermore, GSH reduction in these regions correlated with decline in cognitive functions. Receiver operator characteristics analyses evidenced that hippocampal GSH robustly discriminates between MCI and healthy controls with 87.5% sensitivity, 100% specificity, and positive and negative likelihood ratios (LR+/LR-) of 8.76/0.13, while cortical GSH differentiates MCI and AD with 91.7% sensitivity, 100% specificity, and LR+/LR- of 9.17/0.08. Conclusions The present study provides compelling in vivo evidence that estimation of GSH levels in specific brain regions with MRS constitutes a clinically relevant noninvasive biomarker for MCI and AD.Biological Psychiatry 11/2015; Vol 78(issue 10):702–710. DOI:10.1016/j.biopsych.2015.04.005 · 10.26 Impact Factor
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