Establishing translational neuroimaging tools for quantitative assessment of energy metabolism and metabolic reprogramming in healthy and diseased human brain at 7T

建立转化神经影像工具，用于定量评估 7T 健康和患病人脑的能量代谢和代谢重编程

• 批准号: 10714863
• 负责人: Wei Chen
• 金额: $ 63.02万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714863
• 关键词: ATP phosphohydrolase; Adenosine Triphosphate; Affect; Aging; Area; Biochemical; Bioenergetics; Biomedical Research; Brain; Brain Diseases; Brain Neoplasms; Brain imaging; Cell Respiration; Cerebrovascular Circulation; Cerebrum; Citric Acid Cycle; Clinical; Clinical Research; Collaborations; Complex; Consumption; Creatine Kinase; Deuterium; Diagnosis; Disease; Energy Metabolism; Energy Metabolism Pathway; Engineering; FDA approved; Face; Glucose; Glycolysis; Goals; Health; Homeostasis; Human; Image; Imaging Device; Imaging Techniques; Leadership; Life; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Maps; Measurement; Measures; Mental disorders; Metabolic; Metabolic Pathway; Methods; Mitochondria; Monitor; Motor; NMR Spectroscopy; Neurodegenerative Disorders; Neurons; Neurosciences Research; Nicotinamide adenine dinucleotide; Noise; Nuclear; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen; Oxygen Consumption; Pathway interactions; Patients; Performance; Phosphorus; Physiological; Pilot Projects; Play; Process; Production; Reaction; Research; Research Design; Resolution; Resources; Role; Scanning; Signal Transduction; Stroke; Technology; Testing; Time; Visual; clinical application; detection sensitivity; glucose metabolism; human disease; imaging capabilities; imaging detection; imaging facilities; imaging modality; improved; innovation; insight; kinetic model; member; metabolic imaging; metabolic rate; nervous system disorder; neuroimaging; neurophysiology; next generation; non-invasive imaging; novel; quantitative imaging; radio frequency; response; skills; spatiotemporal; success; temporal measurement; tool; translational applications; translational study; treatment effect; tumor heterogeneity

PROJECT SUMMARY Cellular energy metabolism is a fundamental process of life that produces biochemical energy in the form of adenosine triphosphate (ATP) to support neuronal activity and brain function. Glucose and oxygen are the main energy substrates of the brain and are metabolized through glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation pathways, constituting a neuroenergetic network that effectively regulates ATP production and homeostasis. ATP production and homeostasis are affected when brain states change, as signs of altered cerebral glucose and oxidative metabolism are commonly seen in aging, neurodegenerative diseases, psychiatric disorders, stroke and cancer. Despite the important roles of brain energy metabolism, metabolic alteration and reprogramming in health and disease, noninvasive neuroimaging tools capable of mapping and quantifying key features of neuroenergetic network in the human brain are still lacking. Over the past two decades, we have developed three ultrahigh-field (UHF) metabolic imaging techniques based on deuterium-2 (2H), oxygen-17 (17O), and phosphorus-31 (31P) magnetic resonance spectroscopy (MRSI) imaging capable of noninvasive and quantitative assessment of brain energy metabolism along major metabolic pathways. However, X-nuclear MRSI-based methods face severe challenges in translational applications due to low detection sensitivity and metabolite content, and prolonged scanning time. This project aims to develop and integrate multiple cutting-edge technologies to build next generation high- resolution, high-performance and translatable neuroimaging tools on an FDA-approved 7 Tesla clinical scanner for quantitatively imaging key metabolic rates and other essential neurophysiological parameters related to energy metabolism in healthy and diseased human brains. Three pilot studies are proposed to test and demonstrate the utility and feasibility of the novel neuro-metabolic imaging tools to quantitatively study neuroenergetics and metabolic reprogramming in brain activation, aging processes and brain tumors, aiming to understand their critical roles in brain function and disease. This project leverages the interdisciplinary expertise of an outstanding team leading in the research field, excellent imaging facilities and resources, and close collaboration among team members. The advanced neuroimaging tools established by this project is expected to have significant impact on changing the paradigm of neurometabolic imaging and energy metabolism research, and enable translational studies of human brain bioenergetics and metabolic reprogramming under physiopathological conditions.

项目摘要 细胞能量代谢是生命的基本过程，以形式产生生化能量 三磷酸腺苷（ATP）支持神经元活性和脑功能。葡萄糖和氧气是 大脑的主要能量底物，并通过糖酵解，三羧酸周期和 氧化磷酸化途径，构成有效调节ATP的神经烯网络 生产和稳态。当大脑状态改变时，ATP的产生和稳态会受到影响 脑葡萄糖改变的迹象和氧化代谢通常在衰老，神经退行性中观察到 疾病，精神疾病，中风和癌症。尽管大脑能量代谢的重要作用，但 健康和疾病中的代谢改变和重编程，无创神经影像学工具 仍然缺乏人脑中神经网络的映射和量化关键特征。 在过去的二十年中，我们开发了三个超高场（UHF）代谢成像技术 基于氘-2（2H），氧气17（17o）和磷-31（31p）磁共振光谱法 （MRSI）能够对大脑能量代谢进行非侵入性和定量评估的成像 代谢途径。但是，基于X-核MRSI的方法在翻译方面面临严重的挑战 由于检测敏感性低和代谢物含量以及延长扫描时间而引起的应用。 该项目旨在开发和集成多种尖端技术，以建立下一代高级技术 在FDA批准的7 Tesla临床扫描仪上的分辨率，高性能和可翻译的神经影像学工具 用于定量成像关键代谢率和其他与之相关的基本神经生理参数 健康和患病的人大脑中的能量代谢。提出了三项试点研究进行测试和 展示新型神经代谢成像工具的实用性和可行性来定量研究 脑部激活，衰老过程和脑肿瘤中的神经生能和代谢重编程，旨在 了解它们在大脑功能和疾病中的关键作用。该项目利用跨学科 在研究领域领导的杰出团队的专业知识，出色的成像设施和资源以及 团队成员之间的密切合作。该项目建立的高级神经影像学工具是 预计将对改变神经代谢成像和能量的范式产生重大影响 代谢研究，并启用人脑生物能学和代谢的翻译研究 在生理病理条件下进行重新编程。