Currently, the only widely available metabolic imaging technique in the clinic is positron emission tomography (PET) detection of the radioactive glucose analog 2-¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸FDG). However, ¹⁸FDG-PET does not inform on metabolism downstream of glucose uptake and often provides ambiguous results in organs with intrinsic high glucose uptake, such as the brain. Deuterium metabolic imaging (DMI) is a novel, noninvasive approach that combines deuterium magnetic resonance spectroscopic imaging with oral intake or intravenous infusion of nonradioactive ²H-labeled substrates to generate three-dimensional metabolic maps. DMI can reveal glucose metabolism beyond mere uptake and can be used with other ²H-labeled substrates as well. We demonstrate DMI by mapping metabolism in the brain and liver of animal models and human subjects using [6,6′-²H₂]glucose or [²H₃]acetate. In a rat glioma model, DMI revealed pronounced metabolic differences between normal brain and tumor tissue, with high-contrast metabolic maps depicting the Warburg effect. We observed similar metabolic patterns and image contrast in two patients with a high-grade brain tumor after oral intake of ²H-labeled glucose. Further, DMI used in rat and human livers showed [6,6′-²H₂]glucose stored as labeled glycogen. DMI is a versatile, robust, and easy-to-implement technique that requires minimal modifications to existing clinical magnetic resonance imaging scanners. DMI has great potential to become a widespread method for metabolic imaging in both (pre)clinical research and the clinic.

The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using ¹³C MR spectroscopy in combination with infusion of a ¹³C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of ¹³C–beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism.