Age-associated change in pyruvate metabolism investigated with hyperpolarized 13 C-MRI of the human brain

Abstract

In this study, hyperpolarized ¹³ C MRI (HP-¹³ C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized ¹³ C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of ¹³ C-lactate and ¹³ C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized ¹³ C-lactate and normalized ¹³ C-bicarbonate production with age: $-7\%\pm 2\%$ per decade for ¹³ C-lactate and $-9\%\pm 4\%$ per decade for ¹³ C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat ¹³ C-lactate versus age and a slightly increasing ¹³ C-bicarbonate versus age. The results show that both the production of lactate (visible as ¹³ C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as ¹³ C-bicarbonate signal) decrease with age and that the rate of change varies by brain region.

Keywords: MRI; aerobic glycolysis; aging; carbon-13; lactate; metabolism; parcellation.