Using Hyperpolarized [2-¹³C] Dihydroxyacetone to Detect Hepatic Gluconeogenesis

Diabetes afflicts millions of people worldwide and contributes to elevated risk of cardiovascular disease and stroke. Imaging of hepatic metabolic activity using MRI could prove advantageous for diagnosis, treatment monitoring, etc. With the advent of hyperpolarized (HP) carbon-13 based MRI, rapid imaging of metabolic flux is feasible without the use of ionizing radiation.

In this work, we have utilized HP [2-¹³C]dihydroxyacetone (DHA) to observe hepatic metabolism in real time in a perfused mouse (C57BLKS/J) liver model. We have utilized fatty acids and a 1:10 ratio of pyruvate to lactate in the perfusate to mimic physiological conditions. Figure 1 shows the various metabolites observed following the injection of DHA. Ratios of integrals of three-carbon intermediates and hexose sugars (and phosphates) are used to determine the rate of gluconeogenesis. Hepatic gluconeogenic rates are measured in parallel with gold standard tracer methods, confirming the accuracy of HP imaging.

Figure 1: Representative ¹³C NMR spectrum (sum) of hyperpolarized [2-¹³C] DHA metabolism in perfused liver at 14.1 T. Spectra were measured without ¹H decoupling. Phosphoenolpyruvate (PEP) and glycerol-3-phosphate (G3P) are observed. Note that PEP is normally considered a low concentration metabolites, but it is easily detected here.

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