Hyperpolarized ¹³C magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: First investigations in a large animal model

Early biomarkers of cerebral damage are essential for accurate prognosis, timely intervention, and evaluation of new treatment modalities in newborn infants with hypoxia and ischemia at birth. Hyperpolarized C-13 magnetic resonance imaging (MRI) is a novel method with which to quantify metabolism in vivo with unprecedented sensitivity. We aimed to investigate the applicability of hyperpolarized C-13 MRI in a newborn piglet model and whether this method may identify early changes in cerebral metabolism after a standardized hypoxic-ischemic (HI) insult. Six piglets were anesthetized and subjected to a standardized HI insult. Imaging was performed prior to and 2 h after the insult on a 3-T MR scanner. For C-13 studies, [1-C-13]pyruvate was hyperpolarized in a commercial polarizer. Following intravenous injection, images were acquired using metabolic-specific imaging. HI resulted in a metabolic shift with a decrease in pyruvate to bicarbonate metabolism and an increase in pyruvate to lactate metabolism (lactate/bicarbonate ratio, mean [SD]; 2.28 [0.36] vs. 3.96 [0.91]). This is the first study to show that hyperpolarized C-13 MRI can be used in newborn piglets and applied to evaluate early changes in cerebral metabolism after an HI insult.