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Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia

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Abstract

Objective: Quantitation of glutathione (GSH) in the human brain in vivo using short echo time 1 H NMR spectroscopy is challenging because GSH resonances are not easily resolved. The main objective of this study was to validate such quantitation in a clinically relevant population using the resolved GSH resonances provided by edited spectroscopy. A secondary objective was to compare several of the neurochemical concentrations quantified along with GSH using LCModel analysis of short echo time spectra in schizophrenia versus control.

Materials and Methods: GSH was quantified at 4T from short echo STEAM spectra and MEGA-PRESS edited spectra from identical volumes of interest (anterior cingulate) in ten volunteers. Neurochemical profiles were quantified in nine controls and 13 medicated schizophrenic patients.

Results: GSH concentrations as quantified using STEAM, 1.6 ± 0.4 μmol/g (mean ± SD, n=10), were within error of those quantified using edited spectra, 1.4 ± 0.4 μmol/g, and were not different (p=0.4). None of the neurochemical measurements reached sufficient statistical power to detect differences smaller than 10% in schizophrenia versus control. As such, no differences were observed.

Conclusions: Human brain GSH concentrations can be quantified in a clinical setting using short-echo time STEAM spectra at 4T.

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References

  • Gruetter R, Weisdorf SA, Rajamayagan V, Terpstra M, Merkle H, Truwit CL, Garwood M, Nyberg SL, Ugurbil K (1998) Resolution Improvements in in vivo 1 H NMR spectra with increased magnetic field strength. J Magn Reson 135:260–264

    Article  PubMed  CAS  Google Scholar 

  • Ugurbil K, Adriany G, Andersen P, Chen W, Garwood M, Gruetter R, Henry P-G, Kim S-G, Lieu H, Tkac I, Vaughan T, Van De Moortele P-F, Yacoub E, Zhu X-H (2003) Ultrahigh field magnetic resonance imaging and spectroscopy. Magn Reson Imaging 21:1263–1281

    Article  PubMed  Google Scholar 

  • Pfeuffer J, Tkac I, Provencher SW, Gruetter R (1999) Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time 1H NMR spectra of the rat brain. J Magn Reson 141:104–120

    Article  PubMed  CAS  Google Scholar 

  • Trabesinger AH, Weber OM, Duc CO, Boesiger P (1999) Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering. Magn Reson Med 42:283–289

    Article  PubMed  CAS  Google Scholar 

  • Terpstra M, Henry P-G, Gruetter R (2003) Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference edited spectra. Magn Reson Med 50:19–23

    Article  PubMed  CAS  Google Scholar 

  • Kudo H, Mio T, Kokunai T, Tamaki N, Sumino K, Matsumoto S (1990) Quantitative analysis of glutathione in human brain tumors. J Neurosurg 72:610–615

    Article  PubMed  CAS  Google Scholar 

  • Cooper AJL (1998) Role of astrocytes in maintaining cerebral glutathione homeostasis and in protecting the brain against xenobiotocs and oxidative stress. In: Shaw CA. (ed). Glutathione in the nervous system. Taylor& Francis, London, pp. 91–115

    Google Scholar 

  • Kosower EM (1976) Chemical properties of glutathione. In: Arias JM, Jacoby WB. (ed). Glutathione: metabolism and function. Raven Press, New York, pp. 1–15

    Google Scholar 

  • Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuenod M (2000) Schizophrenia: glutathione deficit in cerebrospinal fluid and prefontal cortex in vivo. Eur J Neurosci 12:3271–3278

    Article  Google Scholar 

  • Rice ME, Russo-Menna I (1998) Differential compartemtalization of brain ascorbate and glutathione between neurons and glia. Neuroscience 82:1213–1223

    Article  PubMed  CAS  Google Scholar 

  • Mukerjee S, Mahadik SP, Scheffer R, Corenti EE, Kelkar H (1996) Impaired antioxidant defense at the onset of psychosis. Schizo Res 19:19–26

    Article  CAS  Google Scholar 

  • Buckman T, Kling A, Sutphin M, Steinberg A, Eiduson S (1990) Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables. Psychiatry Res 31:1–14

    Article  PubMed  CAS  Google Scholar 

  • Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC (2002) Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 159:1944–1946

    Article  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured clinical interview for DSM-IV axis 1 disorders. American Psychiatric Press, Washington

    Google Scholar 

  • Gruetter R, Tkac I (2000) Field mapping without reference scan using asymmetric echo-planar techniques. Magn Reson Med 43:319–323

    Article  PubMed  CAS  Google Scholar 

  • Tkac I, Starcuk Z, Choi I-Y, Gruetter R (1999) In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Mang Reson Med 41:649–656

    Article  CAS  Google Scholar 

  • Seaquist ER, Damberg GS, Tkac I, Gruetter R (2001) The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes 50:2203–2209

    Article  PubMed  CAS  Google Scholar 

  • Tkac I, Gruetter R (2005) Methodology of 1 H NMR spectroscopy of the human brain at very high magnetic fields. Appl Magn Reson 29:139–157

    Article  CAS  Google Scholar 

  • Provencher S (2000) Concentration table. In: Provencher S. (ed). LCModel & LCMgui User’s Manual, pp 12

  • Bartha R, Drost DJ, Menon RS, Williamson PC (2000) Comparison of the quantification precision of human short echo time 1H spectroscopy at 1.5 and 4.0 T. Magn Reson Med 44:185–192

    Article  Google Scholar 

  • Adams JJ, Klaidman L, Odunze I, Shen H, Miller C (1991) Alzheimer’s and Parkinson’s disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Mol Chem Neuropathol 14:213–226

    Article  PubMed  CAS  Google Scholar 

  • Slivka A, Spina M, Cohen G (1987) Reduced and oxidized glutathione in human and monkey brain. Neurosci Lett 74:112–118

    Article  PubMed  CAS  Google Scholar 

  • Reiderer P, Sofic E, Rausch W-D, Schmidt B, Reynolds GP, Jellinger K, Youdim MBH (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52:515–520

    Article  PubMed  Google Scholar 

  • Pae C-U, Choe B-Y, Joo R-H, Lim H-K, Kim T-S, Yoo S-S, Choi B-G, Kim J-J, Lee S-J, Lee C, Paik I-H, Lee CU (2004) Neuronal dysfunction of the frontal lobe in schizophrenia. Neuropsychobiology 50:211– 215

    Article  PubMed  Google Scholar 

  • Molina V, Sanchez J, Reig S, Sanz J, Benito C, Santamarta C, Pascau J, Sarramea F, Gisbert JD, Misiego JM, Palomo T, Desco M (2005) N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration. Schizo Res 73:209–219

    Article  Google Scholar 

  • Ohrmann P, Seigmund A, Suslow T, Spitzberg K, Kersting A. Arolt V, Heindel W, Pfleiderer B (2005) Evidence for glutamatergic neuronal dysfunction in prefrontal cortex in chronic but not first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizo Res 73:153–157

    Article  Google Scholar 

  • Hetherington HP, Pan JW, Spencer DD (2002) 1 H and 31 P spectroscopy and bioenergetics in the lateralization of seizures in temporal lobe epilepsy. J Magn Reson Imaging 16:477–483

    Article  PubMed  Google Scholar 

  • Danielsen ER, Michaelis T, Ross BD (1995) Three methods of calibration in quantitative proton MR spectroscopy. J Magn Reson Ser B106:287–291

    Article  CAS  Google Scholar 

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Correspondence to Melissa Terpstra.

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Terpstra, M., Vaughan, T.J., Ugurbil, K. et al. Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia. MAGMA 18, 276–282 (2005). https://doi.org/10.1007/s10334-005-0012-0

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  • DOI: https://doi.org/10.1007/s10334-005-0012-0

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