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.

项目摘要 氘磁共振成像，氘，已被证明有能力识别大脑的变化， 与癌症相关的代谢。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 挑战性这项工作假定，[2 H7]葡萄糖代谢后HDO的成像将产生更多的 灵敏的检测手段糖酵解和葡萄糖氧化的克雷布斯循环。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峰值的高信噪比允许简单的梯度回波方法被应用于 用于检测，促进图像中更高的空间分辨率。在体内注射[2 H7]葡萄糖后， 存在约15分钟的窗口，其中HDO外观几乎完全匹配氘代glx的生成， 表明HDO可以作为脑中氧化通量的替代物。充分利用这一 窗口，我们将开发压缩传感方法，用于加速2 H图像的采集。HDO是 自由扩散，并且在很长一段时间内，我们认为大脑中过多的HDO出现与血管HDO有关 由外周代谢产生。我们将使用弥散加权成像来检验假设， 血管HDO信号的抑制将使剩余的HDO组分成为以下的忠实报告者： 脑葡萄糖代谢我们将比较我们的新方法与8 F-脱氧葡萄糖-正电子发射 断层扫描（FDG-PET），以确定这两种技术是否提供了关于 在脑癌动物模型中的代谢。本提案的总体目标是建立HDO成像， 大脑葡萄糖代谢的一个强有力的标志物。 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， 认知科学，病理生理学的研究，并在临床诊断的多个脑相关 疾病目前用于代谢脑成像的主要方法是FDG-PET， 由于总辐射暴露指南，纵向研究或儿科人群。 开发一种基于磁共振的方法，可以安全地重复使用， 增强了我们在神经科学中研究大脑功能的能力本文所述的基础研究 该提案将提高一种新的方法的鲁棒性，该方法用于基于对脑代谢的检测来检测脑代谢。 全氘代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最合适的发展基质。