Noninvasive quantification of T2 and concentrations of ascorbate and glutathione in the human brain from the same double-edited spectra

Abstract

The transverse relaxation times (T(2)) and concentrations of Ascorbate (Asc) and glutathione (GSH) were measured from a single dataset of double-edited spectra that were acquired at several TEs at 4 T in the human brain. Six TEs between 102 and 152 ms were utilized to calculate T(2) for the group of 12 subjects scanned five times each. Spectra measured at all six TEs were summed to quantify the concentration in each individual scan. LCModel fitting was optimized for the quantification of the Asc and GSH double-edited spectra. When the fitted baseline was constrained to be flat, T(2) was found to be 67 ms (95% confidence interval, 50-83 ms) for GSH and ≤115 ms for Asc using the sum of spectra measured over 60 scans. The Asc and GSH concentrations quantified in each of the 60 scans were 0.62 ± 0.08 and 0.81 ± 0.11 µmol/g [mean ± standard deviation (SD), n = 60], respectively, using 10 µmol/g N-acetylaspartate as an internal reference and assuming a constant influence of N-acetylaspartate and antioxidant T(2) relaxation in the reference solution and in vivo. The T(2) value of GSH was measured for the first time in the human brain. The data are consistent with short T(2) for both antioxidants. These T(2) values are essential for the absolute quantification of Asc and GSH concentrations measured at long TE, and provide a critical step towards addressing assumptions about T(2), and therefore towards the quantification of concentrations without the possibility of systematic bias.