title: MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis.
abstract: Detection of glutathione (GSH) is technically challenging at clinical field strengths of 1.5 or 3 T due to its low concentration in the human brain coupled with the fact that conventional single-echo acquisitions, typically used for magnetic resonance (MR) spectroscopy acquisitions, cannot be used to resolve GSH given its overlap with other resonances. In this study, an MR spectral editing scheme was used to generate an unobstructed detection of GSH at 7 T. This technique was used to obtain normative white (WM) and gray matter (GM) GSH concentrations over a two-dimensional region. Results indicated that GSH was significantly higher (P<.001) in GM relative to WM in normal subjects. This finding is consistent with previous radionuclide experiments and histochemical staining and validates this 7 T MR spectroscopy technique. To our knowledge, this is the first study to report normative differences in WM and GM glutathione concentrations in the human brain. Glutathione is a biomarker for oxidative status and this non-invasive in vivo measurement of GSH was used to explore its sensitivity to oxidative state in multiple sclerosis (MS) patients. There was a significant reduction (P<.001) of GSH between the GM in MS patients and normal controls. No statistically significant GSH differences were found between the WM in controls and MS patients. Reduced GSH was also observed in a MS WM lesion. This preliminary investigation demonstrates the potential of this marker to probe oxidative state in MS.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94107-1739, USA. radhika.srinivasan@radiology.ucsf.edu
authors.forename: Radhika
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Helene
authors.initials: H
authors.lastname: Ratiney
authors.forename: Kathyrn E
authors.initials: KE
authors.lastname: Hammond-Rosenbluth
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D005978:Glutathione