Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer

Simon Hu, Peder E.Z. Larson, Mark VanCriekinge, Andrew M. Leach, Ilwoo Park, Christine Leon, Jenny Zhou, Peter J. Shin, Galen Reed, Paul Keselman, Cornelius Von Morze, Hikari Yoshihara, Robert A. Bok, Sarah J. Nelson, John Kurhanewicz, Daniel B. Vigneron

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of 13C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-13C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5min interval between injections of hyperpolarized [1-13C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1min after administration, and 6min after administration. Dramatic increases in 13C-bicarbonate were detected just 1min (as well as 6min) after DCA administration.

Original languageEnglish
Pages (from-to)490-496
Number of pages7
JournalMagnetic Resonance Imaging
Volume31
Issue number4
DOIs
StatePublished - May 1 2013
Externally publishedYes

Keywords

  • Dichloroacetate (DCA)
  • Dynamic nuclear polarization (DNP)
  • Hyperpolarized carbon-13
  • Pyruvate metabolism
  • SpinLab™ prototype

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    Hu, S., Larson, P. E. Z., VanCriekinge, M., Leach, A. M., Park, I., Leon, C., Zhou, J., Shin, P. J., Reed, G., Keselman, P., Von Morze, C., Yoshihara, H., Bok, R. A., Nelson, S. J., Kurhanewicz, J., & Vigneron, D. B. (2013). Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer. Magnetic Resonance Imaging, 31(4), 490-496. https://doi.org/10.1016/j.mri.2012.09.002