HDO Imaging is a Quantitative Marker of Cerebral Glucose Oxidation

HDO 成像是脑葡萄糖氧化的定量标志物

• 批准号: 10687186
• 负责人: James A Bankson
• 金额: $ 54.79万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687186
• 关键词: Acceleration; Address; Agreement; Animal Model; Appearance; Area; Basic Science; Biochemistry; Biological; Biological Markers; Blood Vessels; Brain; Brain imaging; Calibration; Cancer Detection; Cancer Model; Carbon; Cerebrum; Chemical Shift Imaging; Chemicals; Childhood; Citric Acid Cycle; Clinical; Cognition; Complex; Consumption; Contrast Media; Data; Deoxyglucose; Detection; Deuterium; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dose; Electromagnetic Energy; Face; Functional disorder; Future; Generations; Glucose; Glucose tolerance test; Glutamates; Glutamine; Glycolysis; Goals; Guidelines; Hour; Hybrids; Image; Injections; Intracellular Space; Ionizing radiation; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Metabolic; Metabolism; Methods; Modeling; Neurosciences; Noise; Pediatric Oncology; Peripheral; Population; Positron-Emission Tomography; Production; Radiation exposure; Relaxation; Reporter; Reporting; Research; Resolution; Sampling; Science; Signal Transduction; Site; Specificity; Sprague-Dawley Rats; Techniques; Testing; Time; Tissues; Tracer; Validation; Work; brain dysfunction; brain metabolism; brain research; clinical diagnosis; detection method; dosage; experimental study; fluorodeoxyglucose positron emission tomography; glucose metabolism; glucose uptake; imaging agent; imaging approach; imaging modality; improved; in vivo; inhibitor; insight; insulin sensitivity; interest; metabolic imaging; multiparametric imaging; oxidation; reconstruction; response; spectroscopic imaging; success; targeted imaging; tumor

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.

项目概要 氘核磁共振成像 (DMI) 已被证明能够识别大脑变化 新陈代谢与癌症有关。然而，葡萄糖代谢的下游产物， 谷氨酸/谷氨酰胺 (glx) 和乳酸本质上具有较低的信噪比，因此无法进行检测 具有挑战性的。这项工作假设 [2H7] 葡萄糖代谢后 HDO 成像将产生更多 检测克雷布斯循环中糖酵解和葡萄糖氧化的灵敏方法。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脑代谢的影响 葡萄糖底物。 HDO 峰的高信噪比允许简单的梯度回波方法 用于检测，促进图像的更高空间分辨率。体内注射[2H7]葡萄糖后， 存在大约 15 分钟的窗口，其中 HDO 外观几乎与氘代 glx 的生成完全匹配， 表明 HDO 可以作为大脑氧化通量的替代物。为了充分利用这一点 在这个窗口中，我们将开发压缩传感方法来加速 2H 图像的采集。 HDO 是 可自由扩散，长期以来我们认为大脑中过量的 HDO 与血管 HDO 有关 由外周代谢产生。我们将使用扩散加权成像来检验以下假设： 血管 HDO 信号的抑制将使剩余的 HDO 成分成为忠实的报告者 脑葡萄糖代谢。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) 以确定这两种技术是否提供了互补信息 脑癌动物模型中的代谢。该提案的总体目标是将 HDO 成像建立为 脑葡萄糖代谢的有力标志物。 关联 大脑的代谢成像在所有神经科学中都受到普遍关注，从基础生物化学到 认知科学、病理生理学研究以及多种脑相关疾病的临床诊断 疾病。目前用于代谢脑成像的主要方法是FDG-PET，无法使用 根据总辐射暴露指南，用于纵向研究或儿科人群。 开发一种可安全重复使用的基于磁共振的方法将显着 增强我们在整个神经科学领域研究大脑功能的能力。本文描述的基础研究 该提案将提高基于检测的脑代谢新方法的鲁棒性 全氘化葡萄糖示踪剂代谢后的 HDO。葡萄糖是用于能量的主要底物 在大脑中产生，因此是在这种情况下发育的最合适的基质。