Abstract
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 13C-glucose MRS and non-hyperpolarized 2H-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 13C-glucose and non-hyperpolaized 2H-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 13C-glucose reports on de novo lactate synthesis and is sensitive to cerebral metabolic rate of glucose (CMRGlc). We show that variations in cerebral glucose metabolism, under different anesthesia, are reflected differently in hyperpolarized and non-hyperpolarized X-nuclei glucose MRS.
Highlights
The mammalian brain is mainly supported by glucose (Glc) as fuel to meet its high metabolic demand [1], consuming up to 25% of circulating Glc under normal conditions [2]
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
We show that variations in cerebral glucose metabolism, under different anesthesia, are reflected differently in hyperpolarized and non-hyperpolarized X-nuclei glucose magnetic resonance spectroscopy (MRS)
Summary
The mammalian brain is mainly supported by glucose (Glc) as fuel to meet its high metabolic demand [1], consuming up to 25% of circulating Glc under normal conditions [2]. Various techniques are available to study in vivo glycolytic metabolism non-invasively, giving complementary information on the metabolic pathways of Glc. Positron emission tomography (PET) of the radioactive 18F labeled fluorodeoxyglucose (FDG) [9,10], widely employed clinically, is capable to monitor uptake of this Glc analog with high sensitivity and good spatial resolution. Magnetic resonance spectroscopy (MRS) measurements of non-hyperpolarized (non-HP; i.e., thermally polarized) 13C labeled Glc bring important kinetic information on brain metabolism with low background signal, and it enabled to demonstrate the compartmentation of the cerebral Glc metabolism between the neurons and the glia [16]. Its low sensitivity necessitates long acquisition times and long infusion times, which makes it difficult to apply for human studies and not suitable for clinical applications, despite being an interesting preclinical research tool providing extensive biochemical information on brain metabolism in vivo. Implementation of MRSI following infusion of non-HP [6,6 -2H2] Glc has shown its large potential by enabling imaging of Glc metabolism in the human brain [18] and may open new avenues for clinical diagnostic
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