Metabolic Imaging Of Acute Lung Injury Using Hyperpolarzied 13c Magnetic Resonance Imaging

This project’s main objective was to develop and implement a molecular imaging tool based on hyperpolarized 13C magnetic resonance imaging (MRI) to quantitatively interrogate lung metabolism. The pulmonary system plays a major role in performing a variety of biochemical functions that maintain body homeostasis, but that undergo significant detrimental alteration in the setting of lung injury and/or inflammation. Such changes cause lactic acid to be released from the lungs and are associated with increased patient mortality. The ability to directly measure both changes in lung metabolism and its spatial heterogeneity can provide insight into the relationship between abnormal mechanics and cellularity in diseased lung tissue. This work primarily focuses on small and large mammalian species as a stepping stone toward translation to human subjects. The key deliverables of this project are acquisition and quantification tools for the regional assessment of hyperpolarized pyruvate’s conversion to lactate in lung tissue. To demonstrate the utility of our method, we used a two-hit animal model of acid aspiration and ventilator-induced lung injury that mimics a variety of inflammatory pulmonary diseases including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We measure the conversion of pyruvate to lactate using hyperpolarized lactate-to-pyruvate ratio, and show that this ratio is significantly correlated with inflammatory activity in the lung tissue as well as the degree of systemic hypoxemia. To further investigate hypoxia’s contribution to increased pulmonary lactate production, we assessed overall lung metabolism in non-injured hypoxic animals: while pulmonary pyruvate metabolism is resilient to moderate levels of hypoxemia, it changes significantly as a result of severe hypoxemia. Our data suggest that the increased lactate-to-pyruvate ratio in injured lungs is predominantly caused by inflammation. Next, we used our techniques to image both healthy and injured pigs on a clinical scanner in order to demonstrate the potential clinical translatability of hyperpolarized 13C imaging. Finally, we explored the possibility of using other imaging pulse sequences to achieve higher spatial and temporal resolution in both small and large animals, concluding that our method can serve as a future basis for rapid, high-resolution metabolic imaging of the lungs