Changes in levels of the antioxidant glutathione in brain and blood across the age span of healthy adults: A systematic review.

Aging is characterized by a gradual decline of the body's biological functions, which can lead to increased production of reactive oxygen species (ROS). Antioxidants neutralize ROS and maintain balance between oxidation and reduction. If ROS production exceeds the ability of antioxidant systems to neutralize, a damaging state of oxidative stress (OS) may exist. The reduced form of glutathione (GSH) is the most abundant antioxidant, and decline of GSH is considered a marker of OS. Our review summarizes the literature on GSH variations with age in healthy adults in brain (in vivo, ex vivo) and blood (plasma, serum), and reliability of in vivo magnetic resonance spectroscopy (MRS) measurement of GSH. A systematic PubMed search identified 35 studies. All in vivo MRS studies (N = 13) reported good to excellent reproducibility of GSH measures. In brain, 3 out of 4 MRS studies reported decreased GSH with age, measured in precuneus, cingulate, and occipital regions, while 1 study reported increased GSH with age in frontal and sensorimotor regions. In post-mortem brain, out of 3 studies, 2 reported decreased GSH with age in hippocampal and frontal regions, while 1 study reported increased GSH with age in a frontal region. Oxidized glutathione disulfide (GSSG) was reported to be increased in caudate with age in 1 study, suggesting OS. Although findings in the brain lacked a clear consensus, the majority of studies suggested a decline of GSH with age. The low number of studies (particularly ex vivo) and potential regional differences may have contributed to variability in the findings in brain. In blood, in contrast, GSH levels predominately were reported to decrease with advancing age (except in the oldest-old, who may represent a select group of particularly successful agers), while GSSG findings lacked consensus. The larger number of studies assessing age-specific GSH level changes in blood (N = 16) allowed for more robust consensus across studies than in brain. Overall, the literature suggests that aging is associated with increased OS in brain and body, but the timing and regional distribution of changes in the brain require further study. The contribution of brain OS to brain aging, and the effect of interventions to raise brain GSH levels on decline of brain function, remain understudied. Given that reliable tools to measure brain GSH exist, we hope this paper will serve as a catalyst to stimulate more work in this field.

Retrospective frequency drift correction of rosette MRSI data using spectral registration.

PURPOSE: Frequency drift correction is an important postprocessing step in MRS that yields improvements in spectral quality and metabolite quantification. Although routinely applied in single-voxel MRS, drift correction is much more challenging in MRSI due to the presence of phase-encoding gradients. Thus, separately acquired navigator scans are normally required for drift estimation. In this work, we demonstrate the use of self-navigating rosette MRSI trajectories combined with time-domain spectral registration to enable retrospective frequency drift corrections without the need for separately acquired navigator echoes. METHODS: A rosette MRSI sequence was implemented to acquire data from the brains of 5 healthy volunteers. FIDs from the center of k-space ( k = 0 $$ k=0 $$ FIDs) were isolated from each shot of the rosette acquisition, and time-domain spectral registration was used to estimate the frequency offset of each k = 0 $$ k=0 $$ FID relative to a reference scan (the first k = 0 $$ k=0 $$ FID in the series). The estimated frequency offsets were then used to apply corrections throughout k $$ k $$ -space. Improvements in spectral quality were assessed before and after drift correction. RESULTS: Spectral registration resulted in significant improvements in signal-to-noise ratio (12.9%) and spectral linewidths (18.5%). Metabolite quantification was performed using LCModel, and the average Cramer-Rao lower bounds uncertainty estimates were reduced by 5.0% for all metabolites, following field drift correction. CONCLUSION: This study demonstrated the use of self-navigating rosette MRSI trajectories to retrospectively correct frequency drift errors in in vivo MRSI data. This correction yields meaningful improvements in spectral quality.