Volumetric spiral chemical shift imaging of hyperpolarized [2-13c]pyruvate in a rat c6 glioma model

Jae Mo Park, Sonal Josan, Taichang Jang, Milton Merchant, Ron Watkins, Ralph E. Hurd, Lawrence D. Recht, Dirk Mayer, Daniel M. Spielman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Purpose MRS of hyperpolarized [2-13C]pyruvate can be used to assess multiple metabolic pathways within mitochondria as the 13C label is not lost with the conversion of pyruvate to acetyl-CoA. This study presents the first MR spectroscopic imaging of hyperpolarized [2-13C]pyruvate in glioma-bearing brain. Methods Spiral chemical shift imaging with spectrally undersampling scheme (1042 Hz) and a hard-pulse excitation was exploited to simultaneously image [2-13C]pyruvate, [2-13C]lactate, and [5-13C]glutamate, the metabolites known to be produced in brain after an injection of hyperpolarized [2-13C]pyruvate, without chemical shift displacement artifacts. A separate undersampling scheme (890 Hz) was also used to image [1-13C]acetyl-carnitine. Healthy and C6 glioma-implanted rat brains were imaged at baseline and after dichloroacetate administration, a drug that modulates pyruvate dehydrogenase kinase activity. Results The baseline metabolite maps showed higher lactate and lower glutamate in tumor as compared to normal-appearing brain. Dichloroacetate led to an increase in glutamate in both tumor and normal-appearing brain. Dichloroacetate-induced %-decrease of lactate/glutamate was comparable to the lactate/bicarbonate decrease from hyperpolarized [1-13C]pyruvate studies. Acetyl-carnitine was observed in the muscle/fat tissue surrounding the brain. Conclusion Robust volumetric imaging with hyperpolarized [2-13C]pyruvate and downstream products was performed in glioma-bearing rat brains, demonstrating changes in mitochondrial metabolism with dichloroacetate.

Original languageEnglish (US)
Pages (from-to)973-984
Number of pages12
JournalMagnetic resonance in medicine
Volume75
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • [2-C]pyruvate
  • brain
  • cancer
  • glioma
  • hyperpolarized C
  • mitochondrial metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Park, J. M., Josan, S., Jang, T., Merchant, M., Watkins, R., Hurd, R. E., Recht, L. D., Mayer, D., & Spielman, D. M. (2016). Volumetric spiral chemical shift imaging of hyperpolarized [2-13c]pyruvate in a rat c6 glioma model. Magnetic resonance in medicine, 75(3), 973-984. https://doi.org/10.1002/mrm.25766