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

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.