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

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