HDO Imaging is a Quantitative Marker of Cerebral Glucose Oxidation

项目摘要 氢核磁共振成像，dmi，已经证明有能力识别大脑的变化。 与癌症有关的新陈代谢。然而，葡萄糖代谢的下游产物， 谷氨酸/谷氨酰胺(GLX)和乳酸，具有固有的低信噪比，使检测 很有挑战性。这项工作假设，在[2H7]葡萄糖代谢之后的HDO成像将产生更多 检测Krebs循环中糖酵解和葡萄糖氧化的灵敏手段。为此，我们将 确定底物的最佳剂量水平以及胰岛素敏感性对大脑代谢的影响 葡萄糖底物。HDO峰值的高信噪比允许简单的梯度回波方法 用于检测，有助于提高图像的空间分辨率。体内注射[2H7]葡萄糖后， 存在大约15分钟的窗口，在该窗口中，HDO的出现几乎与氢化GLX的生成完全匹配， 这表明HDO可以作为大脑中氧化通量的替代品。要充分利用这一点 窗口，我们将开发压缩传感方法，以加快获取2H图像。HDO是 在很长一段时间里，我们认为大脑中HDO的过度出现与血管HDO有关 由外周新陈代谢产生。我们将使用扩散加权成像来检验这一假设 血管HDO信号的抑制将使剩余的HDO成分成为 大脑的葡萄糖代谢。我们将把我们的新方法与8F-脱氧葡萄糖-正电子发射进行比较 断层扫描(FDG-PET)以确定两种技术是否提供了互补的信息 脑癌动物模型的代谢。该提案的总体目标是将HDO成像建立为 大脑葡萄糖代谢的强健标记物。 相关性 大脑的代谢成像是所有神经科学的普遍兴趣，从基础生物化学到 认知科学，到病理生理学的研究，以及在多发性脑相关的临床诊断中 疾病。目前用于代谢性脑成像的主要方法是FDG-PET，不能使用 用于纵向研究或由于总辐射暴露指南而在儿科人群中使用。 开发一种基于磁共振的方法，其重复使用是安全的，这将显著地 增强我们在所有神经科学领域研究大脑功能的能力。本文件中描述的基础研究 该提案将提高基于检测脑代谢的新方法的稳健性 高密度脂蛋白跟随过氢葡萄糖示踪剂的新陈代谢。葡萄糖是产生能量的主要底物。 在大脑中产生，因此是在这种情况下最适合发育的底物。

Project Summary Deuterium magnetic resonance imaging, DMI, has demonstrated ability to identify changes in brain metabolism associated with cancer. However, downstream products of glucose metabolism, glutamate/glutamine (glx) and lactate, have intrinsically low signal to noise ratios that make detection challenging. This work posits that imaging of HDO following metabolism of [2H7]glucose will produce a more sensitive means of detecting glycolysis and glucose oxidation in the Krebs cycle. Towards this end we will establish optimal dosing levels of substrate as well as the impact of insulin sensitivity on cerebral metabolism of the glucose substrate. The high signal to noise of the HDO peak allows simple gradient echo methods to be used for detection, facilitating higher spatial resolution in the images. After injection of [2H7]glucose in vivo, a ~15 minute window exists where HDO appearance matches the generation of deuterated glx almost exactly, indicating the HDO can serve as a surrogate of oxidative flux in the brain. To take full advantage of this window, we will develop compressed sensing methods for accelerating acquisition of the 2H images. HDO is freely diffusible, and at long times we believe excess HDO appearance in the brain is related to vascular HDO generated by peripheral metabolism. We will use diffusion weighted imaging to test the hypothesis that suppression of the vascular HDO signal will render the remaining HDO component a faithful reporter of cerebral glucose metabolism. We will compare our new methods to 8F-deoxyglucose - positron emission tomography (FDG-PET) to determine if the two techniques provide complementary information about metabolism in animal models of brain cancer. The overall goal in this proposal is to establish HDO imaging as a robust marker of cerebral glucose metabolism. Relevance Metabolic imaging of the brain is of general interest across all of neuroscience, from basic biochemistry, to cognition science, to the study of pathophysiologies, and in the clinical diagnoses of multiple brain related diseases. The primary method currently used for metabolic brain imaging is FDG-PET, which cannot be used for longitudinal studies or in the pediatric population due to guidelines for total radiation exposure. Development of a magnetic resonance based method, which is safe for repeated use, would significantly enhance our ability to study brain function across all of neuroscience. The basic research described in this proposal will improve the robustness of a new method for detecting brain metabolism based on the detection of HDO following metabolism of a perdeuterated glucose tracer. Glucose is the primary substrate used for energy production in the brain, and is therefore the most appropriate substrate for development in this context.