Hyperpolarized [1- 13 C] pyruvate as a possible diagnostic tool in liver disease

Abstract

Introduction of hyperpolarized magnetic resonance in preclinical studies and lately translation to patients provides new detailed in vivo information of metabolic flux in organs. Hyperpolarized magnetic resonance based on 13 C enriched pyruvate is performed without ionizing radiation and allows quantification of the pyruvate conversion products: alanine, lactate and bicarbonate in real time. Thus, this methodology has a promising potential for in vivo monitoring of energetic alterations in hepatic diseases. Using 13 C pyruvate, we investigated the metabolism in the porcine liver before and after intravenous injection of glucose. The overall mean lactate to pyruvate ratio increased significantly after the injection of glucose whereas the bicarbonate to pyruvate ratio was unaffected, representative of the levels of pyruvate entering the tricarboxylic acid cycle. Similarly, alanine to pyruvate ratio did not change. The increased lactate to pyruvate ratio over time showed an exponential correlation with insulin, glucagon and free fatty acids. Together, these data, obtained by hyperpolarized 13 C magnetic resonance spectroscopy and by blood sampling, indicate a hepatic metabolic shift in glucose utilization following a glucose challenge. Our findings demonstrate the capacity of hyperpolarized 13 C magnetic resonance spectroscopy for quantifying hepatic substrate metabolism in accordance with well-known physiological processes. When combined with concentration of blood insulin, glucagon and free fatty acids in the blood, the results indicate the potential of hyperpolarized magnetic resonance spectroscopy as a future clinical method for quantification of hepatic substrate metabolism.