Metabolic Imaging of the Perfused Rat Heart Using Hyperpolarized [1-13C]Pyruvate

Introduction : The recent development of liquid state Dynamic Nuclear Polarization (DNP) techniques has dramatically increased the signal available from C MRS experiments and has opened up new possibilities for metabolic imaging of the heart [1]. Oxidative decarboxylation of DNP hyperpolarized [1-C]pyruvate, mediated by the pyruvate dehydrogenase (PDH) complex, is a critical reaction that produces acetyl-CoA for ATP synthesis and also produces the byproducts NADH and [1C]carbon dioxide (CO2). CO2 is in pH-dependent equilibrium with bicarbonate (HCO3) and observation of HCO3 production has been shown to be an effective biomarker of real-time, in vivo PDH flux [2]. Further, reduction of hyperpolarized [1-C]pyruvate to [1-C]lactate and transamination to [1-C]alanine can be monitored and it has been shown that [1-C]lactate accumulation is a metabolic indicator of cardiac ischaemia [3]. Thus, the capability to visualize these metabolites in vivo allows us to probe metabolic processes that are critical to energy production and the physiological condition of the heart [1]. However, to fully understand the changes observed in vivo it is useful to be able to study a model system where the exact parameters of the system can be carefully controlled. The perfused rat heart has been used as such a model system for many years, but the limitations of a small heart size and the resulting requirement for high spatial resolution have so far prevented metabolic imaging of the perfused heart with hyperpolarized [1-C]pyruvate. In this study, we aimed to demonstrate the feasibility of mapping the spatial distribution of hyperpolarized pyruvate, lactate, alanine and bicarbonate in the perfused rat heart via the implementation of a rapid, high spatial resolution, chemical shift imaging (CSI) approach.