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

The transverse relaxation times (T₂) 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 152ms were utilized to calculate T₂ 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, T₂ was found to be 67ms (95% confidence interval, 50-83ms) for GSH and ≤115ms 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±0.11μmol/g [mean±standard deviation (SD), n=60], respectively, using 10μmol/g N-acetylaspartate as an internal reference and assuming a constant influence of N-acetylaspartate and antioxidant T₂ relaxation in the reference solution and in vivo. The T₂ value of GSH was measured for the first time in the human brain. The data are consistent with short T₂ for both antioxidants. These T₂ 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 T₂, and therefore towards the quantification of concentrations without the possibility of systematic bias.