Quantifying normal human brain metabolism using hyperpolarized [1-13C]pyruvate and magnetic resonance imaging

Abstract

Hyperpolarized ¹³C Magnetic Resonance Imaging (¹³C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-¹³C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of ¹³C images demonstrated ¹³C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k_PL) for exchange of the hyperpolarized ¹³C label between [1-¹³C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s^-1 and the apparent rate constant (k_PB) for the irreversible flux of [1-¹³C]pyruvate to [¹³C]bicarbonate was 0.002 ± 0.002 s^-1. Imaging also revealed that [1-¹³C]pyruvate, [1-¹³C]lactate and [¹³C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-¹³C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.

Keywords: Brain; Carbon-13; Hyperpolarized; MRI; Metabolism; Pyruvate.

Graphical abstract

Fig. 1

The distribution of hyperpolarized signal from the three metabolites within gray and white matter.

Fig. 2

Region of interest analysis and a field map of the healthy brain.

Fig. 3

¹³C spectra acquired through the healthy brain following injection of hyperpolarized pyruvate.

Fig. 4

Dynamic ¹³C spectra from the healthy brain showing the time course of [1–¹³C]pyruvate, [1–¹³C]lactate and [¹³C]bicarbonate.

Fig. 5

IDEAL spiral ¹³C imaging demonstrating metabolite distribution in the healthy human brain.

Fig. 6

Quantitative analysis of metabolism in white and gray matter.