Spatial distribution of hyperpolarized [1-¹³C]pyruvate MRI and metabolic PET in the human brain

Magnetic resonance imaging (MRI) of hyperpolarized (HP) [1-¹³C]pyruvate is a promising method for measuring cerebral energy metabolism in vivo. The substantial increase in signal provided by HP makes it possible to dynamically monitor the conversion of [1-¹³C]pyruvate to [1-¹³C]lactate and [¹³C]bicarbonate. The HP [1-¹³C]lactate signal is commonly associated with glycolic activity, whereas [¹³C]bicarbonate, a by-product of the reaction that forms acetyl-CoA, is linked to oxidative metabolism. However, there is compelling evidence that other factors, such as the concentration of monocarboxylate transporters, influence the production of HP [1-¹³C]lactate. To clarify the processes responsible for producing the topography of HP [1-¹³C]pyruvate and its metabolites, we spatially correlated group-average HP ¹³C MRI images with [¹⁸F]FDG, [¹⁵O]H₂O, [¹⁵O]O₂, and [¹⁵O]CO positron emission topography (PET) images from a separate group of 35 age- and sex-matched adults. We found that [1-¹³C]pyruvate correlated best with cerebral blood volume (CBV), whereas [1-¹³C]lactate and [¹³C]bicarbonate were most strongly associated with cerebral blood flow (CBF), glucose consumption (CMRglc), and oxygen metabolism (CMRO₂). Neither [1-¹³C]lactate nor [¹³C]bicarbonate was correlated with non-oxidative glucose consumption, also known as aerobic glycolysis. These results are consistent with the view that in the healthy brain, the production of [1-¹³C]lactate reflects overall energy metabolism rather than being specific to glycolysis.