Mahar Rohit, Zeng Huadong, Giacalone Anthony, Ragavan Mukundan, Mareci Thomas H, Merritt Matthew E
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Advanced Magnetic Resonance Imaging and Spectroscopy Facility, College of Medicine, University of Florida, Gainesville, Florida, USA.
Magn Reson Med. 2021 Jun;85(6):3049-3059. doi: 10.1002/mrm.28700. Epub 2021 Feb 12.
To determine whether deuterated water (HDO) generated from the metabolism of [ H ]glucose is a sensitive biomarker of cerebral glycolysis and oxidative flux.
A bolus of [ H ]glucose was injected through the tail vein at 1.95 g/kg into Sprague-Dawley rats. A H surface coil was placed on top of the head to record H 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.
The background HDO signal could be detected and imaged before glucose injection. The H NMR spectra showed arrival of [ H ]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.
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.
确定由[H]葡萄糖代谢产生的重水（HDO）是否为脑糖酵解和氧化通量的敏感生物标志物。
以1.95 g/kg的剂量通过尾静脉向Sprague-Dawley大鼠注射一剂[H]葡萄糖。将一个H表面线圈置于头部上方，每1.3分钟记录一次大脑的H谱，以测量葡萄糖摄取以及向HDO、乳酸和谷氨酸/谷氨酰胺的代谢情况。基于梯度回波序列的两点Dixon方法用于选择性重建重水葡萄糖和水（HDO）图像。
在注射葡萄糖之前即可检测到背景HDO信号并对其成像。H NMR谱显示[H]葡萄糖的到达及其代谢呈时间依赖性。HDO与谷氨酸/谷氨酰胺共振的比值在注射后呈现出一种准稳态，其中脑代谢主导了外周代谢产生的HDO的流入。脑波谱分析表明，在适当的准稳态窗口内，HDO的生成与乳酸和谷氨酸/谷氨酰胺的出现呈线性关系。使用梯度回波方法可轻松实现HDO和葡萄糖的选择性成像。
本文首次展示了将HDO的代谢成像作为葡萄糖、乳酸和谷氨酸/谷氨酰胺代谢的标志物。与基于化学位移成像（CSI）的技术相比，使用标准梯度回波序列可有效评估脑葡萄糖代谢，该序列具有更高的平面分辨率。
