The effects of elevated serum lactate on measures of apparent cerebral metabolism and perfusion in the anesthetised rodent brain.

Abstract

Cerebral metabolism is coupled to perfusion and can be probed using a combination of hyperpolarized carbon-13 MRI and perfusion weighted imaging. It is unknown how alterations in serum lactate affect apparent lactate exchange and pyruvate dehydrogenase flux using hyperpolarized 13C MRI, and so this pre-clinical study was designed to assess the sensitivity of MRI to detect changes in perfusion and apparent metabolism in the anesthetized rodent brain due to sodium lactate administration. Results demonstrated significant differences in cerebral blood flow between the saline and sodium L-lactate administered at 0.5 g/kg (112 {+/-} 5 vs 127 {+/-} 2 mL/100g/min), saline and sodium L-lactate administered at 1 g/kg (112 {+/-} 5 vs 90 {+/-} 5 mL/100g/min), and between sodium L-lactate at 0.5 g/kg and sodium L-lactate at 1 g/kg (127 {+/-} 2 vs 90 {+/-} 5 mL/100g/min). There was excellent reproducibility of cerebral perfusion measurements (ICC > 0.95) between observers, indicating high reliability in these results. There were significant differences in [1-13C] lactate:[1-13C] pyruvate between saline vs 0.5 g/kg (0.22 {+/-} 0.05 vs 0.59 {+/-} 0.15) and saline vs 1 g/kg (0.22 {+/-} 0.05 vs 0.62 {+/-} 0.04), but no significant differences in 13C bicarbonate:[1-13C] pyruvate (p = 0.1). In conclusion, perfusion and [1-13C] lactate:[1-13C] pyruvate are sensitive to changes in serum lactate, but 13C bicarbonate:[1-13C] pyruvate were not. This has implications for brain studies using [1-13C] pyruvate, and understanding the impact of serum lactate on clinical hyperpolarised imaging is needed.