Deuterated water imaging of the rat brain following metabolism of [2H7]glucose

Purpose To determine whether deuterated water (HDO) generated from the metabolism of [H-2(7)]glucose is a sensitive biomarker of cerebral glycolysis and oxidative flux. Methods A bolus of [H-2(7)]glucose was injected through the tail vein at 1.95 g/kg into Sprague-Dawley rats. A H-2 surface coil was placed on top of the head to record H-2 spectra of the brain every 1.3 minutes to measure glucose uptake and metabolism to HDO, lactate, and glutamate/glutamine. A two-point Dixon method based on a gradient-echo sequence was used to reconstruct deuterated glucose and water (HDO) images selectively. Results The background HDO signal could be detected and imaged before glucose injection. The H-2 NMR spectra showed arrival of [H-2(7)]glucose and its metabolism in a time-dependent manner. A ratio of the HDO to glutamate/glutamine resonances demonstrates a pseudo-steady state following injection, in which cerebral metabolism dominates wash-in of HDO generated by peripheral metabolism. Brain spectroscopy reveals that HDO generation is linear with lactate and glutamate/glutamine appearance in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose is easily accomplished using a gradient-echo method. Conclusion Metabolic imaging of HDO, as a marker of glucose, lactate, and glutamate/glutamine metabolism, has been shown here for the first time. Cerebral glucose metabolism can be assessed efficiently using a standard gradient-echo sequence that provides superior in-plane resolution compared with CSI-based techniques.

Automated summary

This study demonstrates for the first time the metabolic imaging of HDO as a marker of glucose, lactate, and glutamate/glutamine metabolism. The generation of HDO in the brain is linearly related to the appearance of lactate and glutamate/glutamine in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose can be easily achieved using a gradient-echo method.