title: Detection of an antioxidant profile in the human brain in vivo via double editing with MEGA-PRESS.
abstract: 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 micromol/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.
authors.affiliation: Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota 55455, USA. melissa@cmrr.umn.edu
authors.forename: Melissa
authors.initials: M
authors.lastname: Terpstra
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Marjanska
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Henry
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkác
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000328:Adult; D000465:Algorithms; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009778:Occipital Lobe / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D005978:Glutathione; D001205:Ascorbic Acid