Detection of an antioxidant profile in the human brain in vivo via double editing with MEGA-PRESS

Vitamin C (ascorbate) and glutathione (GSH) are the two most concentrated non-enzymatic antioxidants in the human brain. Double editing with (DEW) MEGA-PRESS at 4T was designed in this study to measure both antioxidants in the same amount of time previously required to measure one. In the occipital lobe of four human subjects, resolved ascorbate (Asc) and GSH resonances were detected repeatedly and simultaneously using DEW MEGA-PRESS. The Asc and GSH concentrations measured using LCModel analysis of DEW MEGA-PRESS spectra were 0.8 +/- 0.1 and 1.0 +/- 0.1 mu mol/g (mean +/- SD), with average Cramer-Rao lower bounds (CRLB) of 10% and 7%, respectively. Aside from the effects of J-modulation at a common echo time (TE), double editing did not compromise sensitivity. To determine the extent to which the oxidized forms of Asc and GSH contribute to DEW MEGA-PRESS spectra in vivo, chemical shifts and coupling constants for dehydroascorbate (DHA) and oxidized glutathione (GSSG) were measured at physiologic pH and temperature. DHA does not contribute to the 3.73 ppm DEW MEGA-PRESS Asc resonance. GSSG contributions to the DEW MEGA-PRESS GSH resonance (3.0 ppm) are negligible under physiologic conditions, and would be evidenced by a distinct GSSG resonance (3.3 ppm) at exceptionally high concentrations.