Bimg-21. deuterium metabolic imaging (dmi), a new, mri-based technique for mapping brain tumor metabolism in vivo

Abstract Deuterium Metabolic Imaging (DMI) combines 3D deuterium (2H) magnetic resonance spectroscopic imaging (MRSI) with administration of a 2H-labeled substrate to map uptake and metabolism of the substrate. DMI has been implemented on a 4 Tesla clinical research MRI scanner, and on an 11.7 Tesla preclinical MRI scanner, and has been used with 2H-labeled glucose, acetate and choline. DMI data are presented as color maps of concentration of the 2H-labeled substrate and its metabolites, overlaid on anatomical MR images. In rat and mouse models of glioblastoma, DMI data acquired at 5 to 8 uL resolution following intravenous 2H-glucose infusion clearly showed the Warburg effect in the tumor lesions. The Warburg effect is indicated by the ratio of 2H-labeled lactate/glutamate+glutamine (Glx). High levels of 2H-labeled lactate and low levels of 2H-labeled Glx are the result of a high rate of glycolysis and low rate of oxidative glucose metabolism. Because DMI detects both glucose and its downstream metabolism, the technique does not suffer from low image contrast with normal brain, as is the case with FDG-PET that detects glucose uptake only. For clinical research studies patients orally consumed 0.75g/kg of 2H-glucose dissolved in water. The observations made in the animal models were confirmed in several patients with recurrent GBM, showing hotspots in the lac/Glx maps (8 mL resolution), coinciding with the area of the tumor lesion. In patients with meningioma, no Warburg effect was detected using DMI. Furthermore, DMI data acquired in a patient with GBM one week after finishing 30 days of radiation therapy, also showed no high levels of 2H-labeled lactate in the lesion. These data indicate that the presence of the Warburg effect could correlate with tumor grade and/or aggressiveness, and that DMI of glucose metabolism could potentially be a biomarker of therapy effect.