Pyruvate to Lactate Metabolic Changes during Neurodevelopment Measured Dynamically Using Hyperpolarized 13C Imaging in Juvenile Murine Brain

Abstract

Hyperpolarized 13C magnetic resonance imaging has recently been used to dynamically image metabolism in vivo. This technique provides the capability to investigate metabolic changes in mouse brain development over multiple time points. In this study, we used 13C magnetic resonance spectroscopic imaging and hyperpolarized 13C-1-labeled pyruvate to analyze its conversion into lactate. We also applied T2-weighted anatomical imaging to examine brain volume changes starting from postnatal day 18 (P18). We combined these results with body weight measurements for a comprehensive interpretation of mouse brain maturation. Both the produced lactate level and pyruvate to lactate conversion rate decreased with increasing age in a linear manner. Total brain volume remained the same after P18, even though body weight continued to grow exponentially. Our results have shown that the rate of metabolism of 13C-1 pyruvate to lactate in brain is high in the young mouse and decreases with age. The brain at P18 is still relatively immature and continues to develop even as the total brain volume remains the same.