Measuring Glycolytic Activity with Hyperpolarized [(2)H(7), U-(13)C(6)] D-Glucose in the Naive Mouse Brain under Different Anesthetic Conditions

Glucose is the primary fuel for the brain; its metabolism is linked with cerebral function. Different magnetic resonance spectroscopy (MRS) techniques are available to assess glucose metabolism, providing complementary information. Our first aim was to investigate the difference between hyperpolarized (13)C-glucose MRS and non-hyperpolarized (2)H-glucose MRS to interrogate cerebral glycolysis. Isoflurane anesthesia is commonly employed in preclinical MRS, but it affects cerebral hemodynamics and functional connectivity. A combination of low doses of isoflurane and medetomidine is routinely used in rodent functional magnetic resonance imaging (fMRI) and shows similar functional connectivity, as in awake animals. As glucose metabolism is tightly linked to neuronal activity, our second aim was to assess the impact of these two anesthetic conditions on the cerebral metabolism of glucose. Brain metabolism of hyperpolarized (13)C-glucose and non-hyperpolaized (2)H-glucose was monitored in two groups of mice in a 9.4 T MRI system. We found that the very different duration and temporal resolution of the two techniques enable highlighting the different aspects in glucose metabolism. We demonstrate (by numerical simulations) that hyperpolarized (13)C-glucose reports on de novo lactate synthesis and is sensitive to cerebral metabolic rate of glucose (CMR(Glc)). We show that variations in cerebral glucose metabolism, under different anesthesia, are reflected differently in hyperpolarized and non-hyperpolarized X-nuclei glucose MRS.