Novel methodology for studing oxidative metabolism

研究氧化代谢的新方法

• 批准号: 7014050
• 负责人: Ravinder Reddy
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-10 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7014050
• 关键词: aerobiosis; brain disorder diagnosis; brain imaging /visualization /scanning; brain metabolism; catalyst; cerebellum; enzyme activity; magnetic resonance imaging; noninvasive diagnosis; oximetry; oxygen consumption; oxygen transport; swine; technology /technique development

DESCRIPTION (provided by applicant): Oxygen consumption provides vital information about neuronal activity. Neurological disorders such as Alzheimer's disease, Parkinson's disease, and schizophrenia are associated with hampered enzymatic activity that catalyzes the reaction of oxidative metabolism. Oxygen consumption also has the potential for detecting regions of viable tissue following cerebral ischemia. Quantitative mapping of cerebral oxygen consumption contributes to the better understanding of the patho-physiology of several neurological disorders. A current method for such measurements is positron emission tomography (PET), which provides a low-resolution image and involves radioactive isotopes. Current 17O magnetic resonance imaging (MRI) based methods, have limitations such as low sensitivity and requirement of invasive procedure and requirement of ultra-high magnetic fields. These limitations, coupled with the high cost of 17O2 gas, limit the applicability of direct 17O MRI methods to small animal studies. Consequently, there are no non-invasive methods for measuring oxygen consumption in humans in vivo combining safety with high spatial and temporal resolution. This proposal deals with the development of an integrated approach that combines an efficient 17O2 gas delivery system with improved, noninvasive, MRI strategies for computing cerebral metabolic rate of oxygen consumption (CMRO2). Specifically, an efficient 17O2 gas delivery system, that reduces the 17O2 gas requirement by an order of magnitude will be designed and optimized for use on large animals and in humans. Efficacy of this system will be tested on a swine model. MRI methods will be designed to measure arterial input function of metabolically produced water (mpH217O) and cerebral blood flow. Finally, the above-mentioned system and MRI techniques will be integrated into an improved MRI strategy for measuring mpH217O to compute CMRO2 in the brain in vivo. Once the aims are accomplished, a noninvasive tool will become available to measure CMRO2 with high spatial resolution, which can be immediately extended to in vivo human studies. This approach will have substantial impact on the both scientific and clinical studies of neurological disorders and in the development and evaluation of novel therapies.

描述（由申请人提供）：耗氧量提供有关神经元活动的重要信息。阿尔茨海默病、帕金森病和精神分裂症等神经系统疾病与催化氧化代谢反应的酶活性受阻有关。耗氧量还具有检测脑缺血后存活组织区域的潜力。脑耗氧量的定量绘图有助于更好地了解几种神经系统疾病的病理生理学。当前用于此类测量的方法是正电子发射断层扫描（PET），它提供低分辨率图像并涉及放射性同位素。目前基于 17O 磁共振成像（MRI）的方法具有灵敏度低、需要侵入性操作以及需要超高磁场等局限性。这些限制，加上 17O2 气体的高成本，限制了直接 17O MRI 方法在小动物研究中的适用性。因此，目前尚无结合安全性与高空间和时间分辨率的非侵入性方法来测量人体体内耗氧量。 该提案涉及开发一种综合方法，将高效的 17O2 气体输送系统与改进的、无创的 MRI 策略相结合，用于计算大脑耗氧代谢率 (CMRO2)。具体来说，将设计和优化一种高效的 17O2 气体输送系统，将 17O2 气体需求量减少一个数量级，用于大型动物和人类。该系统的功效将在猪模型上进行测试。 MRI方法将被设计用于测量代谢产生的水（mpH217O）的动脉输入功能和脑血流量。最后，上述系统和 MRI 技术将集成到改进的 MRI 策略中，用于测量 mpH217O，以计算体内大脑中的 CMRO2。一旦目标实现，将有一种非侵入性工具可用于以高空间分辨率测量 CMRO2，并可立即扩展到人体体内研究。这种方法将对神经系统疾病的科学和临床研究以及新疗法的开发和评估产生重大影响。