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

It is increasingly recognized that early perturbation of energy metabolism might have important implications in management and ultimately the neurological outcome in patients with traumatic brain injury (TBI). At the same time, treatments and screening tools successfully developed in preclinical TBI models have failed to translate to the clinic. As ferrets possess primate-like gyrencephalic brains that may better replicate the human response to neurologic injury, the goal of this study was to noninvasively measure brain energy metabolism after injury in a ferret model of TBI. To this end, metabolic imaging of hyperpolarized (HP) [1-¹³C]pyruvate (Pyr) and its conversion to lactate (Lac) and bicarbonate (Bic) was performed in ferrets before and after combined under-vehicle blast and controlled cortical impact injury. Reduced Bic/Pyr, reflecting reduced pyruvate dehydrogenase activity, was detected 8-10 days post-injury whereas no difference in Lac/Pyr was observed. These results demonstrate the feasibility of using metabolic imaging of HP [1-¹³C]Pyr to measure perturbations in brain energy metabolism in a novel highly translatable animal model of TBI. The method may contribute to both improved understanding of injury mechanisms and more effective drug development.