Physiological Interpretation of the AUC Ratio for Hyperpolarized [1-13C]-Pyruvate

Motivation: The prevalence of the use of AUC ratio as a metric of anaerobic respiration in hyperpolarized pyruvate studies motivates a careful examination of its physiological interpretation. Goal(s): We seek to characterize the lactate to pyruvate AUC ratio as a surrogate for aerobic glycolysis in cancer cells. Approach: A simplified three-compartment kinetic model is proposed and analyzed. The AUC ratio is found from the model for interpretation. Results: The simplified three-compartment model is shown to produce equivalent time curves to the full model. The AUC ratio, parametrized by the simplified model, varies non-linearly with the rate of intracellular lactate production. Impact: The efficacy of hyperpolarized pyruvate as a probe of tumor metabolism relies on an accurate and reproducible quantification and interpretation of acquired signal. We critically examine one of the most commonly used methods of signal interpretation in hyperpolarized pyruvate studies.