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In vivo 1H magnetic resonance spectroscopy of rat brain after valproate administration

Neuroradiology volume 46, pages 363–367 (2004)Cite this article

Abstract

Previous studies have shown that valproate is detectable in vitro by 1H magnetic resonance spectroscopy (MRS) at 1.5 T, whereas in patients on valproate monotherapy, no significant dose-dependent valproate signal could be seen. To investigate whether an increased signal-to-noise ratio as provided by higher valproate doses and increased magnetic field strength would enable detection of valproate in vivo, six Wistar rats were examined using volume-selective 1H MRS at 2.34 T. The spectra were analyzed by fitting a linear superposition of the basis spectra of valproate, brain metabolites, and simulated lipid signals. The analysis revealed no significant signal contributions after valproate administration of up to 330 mg/kg body weight. To analyze how underlying mechanisms, such as potential drug interactions with macromolecules, may affect the valproate signal, additional in vitro spectra of valproate were measured before and after adding albumin. The spectra exhibited a strong decrease of the valproate signal with increasing albumin concentration. The results support the hypothesis that in vivo valproate is bound to a high degree to macromolecules and will therefore not be detectable by 1H MRS.

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Acknowledgement

We thank Ms. J. Pietrowicz for carefully proofreading the manuscript.

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Affiliations

  1. Department of Medical Informatics, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    J. Leib, C. Klingner & J. Bernarding

  2. Department of Medical Informatics, Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany

    J. Leib, J. Braun, C. Klingner & E. Gedat

  3. Department of Radiology and Nuclear Medicine, Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany

    A. Schilling

  4. Department of Neurology, Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany

    S. Seyfert

  5. Department of Physics, TFH (University of Applied Sciences), Berlin, Germany

    W. Vollmann

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  1. J. Leib
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  2. J. Braun
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  3. A. Schilling
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  4. C. Klingner
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  5. S. Seyfert
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  6. W. Vollmann
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  7. E. Gedat
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  8. J. Bernarding
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Correspondence to J. Bernarding.

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Leib, J., Braun, J., Schilling, A. et al. In vivo 1H magnetic resonance spectroscopy of rat brain after valproate administration. Neuroradiology 46, 363–367 (2004). https://doi.org/10.1007/s00234-004-1182-6

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  • DOI: https://doi.org/10.1007/s00234-004-1182-6

Keywords

  • Volume-selective 1H MRS
  • Anticonvulsant drugs
  • In vivo drug monitoring
  • Rat brain