Metabolic Imaging of Hyperpolarized [1-13C]Pyruvate in a Ferret Model of Traumatic Brain Injury

Motivation: Traumatic brain injury (TBI) represents a huge personal and economic burden. However, treatments and screening tools successfully developed in preclinical TBI models have failed to translate to the clinic. Goal(s): To noninvasively measure brain energy metabolism after injury in a ferret model of TBI as ferrets possess primate-like gyrencephalic brains that may better replicate the human response to neurologic injury. Approach: Metabolic imaging of hyperpolarized (HP) [1-13C]pyruvate and its conversion to lactate (Lac) and bicarbonate (Bic) was used in ferrets before and after injury. Results: Reduced Bic/Pyr, reflecting reduced PDH activity, was detected 8-10 days post-injury whereas no difference in Lac/Pyr was observed. Impact: Metabolic imaging of HP [1-13C]pyruvate for the noninvasive investigation of perturbations in brain energy metabolism in a highly translatable animal model of TBI may contribute to both improved understanding of injury mechanisms and more effective drug development.