STUDY OF BRAIN OXIDATIVE METABOLISM BY 17-0 IMAGING

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 现代神经成像技术，如功能磁共振成像和正电子发射断层扫描，为研究大脑功能和人类行为开辟了令人兴奋的新领域。了解成像信号和潜在的脑生理之间的关系变得越来越重要和紧迫。尽管已经获得了关于神经血管耦合的巨大见解，但脑代谢能量和神经元活动之间的定量关系（即，神经代谢偶联）。特别重要和激烈争论的问题是需要增加多少脑氧代谢率（CMRO 2），或者可以由大脑提供以支持任务诱发的神经元活动。在这方面的主要挑战是缺乏一种快速，非侵入性和定量的方法，能够直接成像绝对CMRO 2在基础和激活的大脑状态。我们在第一个资助周期内成功开发的CMRO 2高场17 O MRS成像（MRSI）方法可以克服这一障碍。这种创新和独特的方法为研究神经代谢耦合及其对大脑功能的影响提供了一个千载难逢的机会。我们的大量初步结果不仅证明了这种基于17 O的CMRO 2成像方法的可行性，可靠性和适用性，而且还提供了关键证据，表明大脑氧化代谢在休息和激活期间支持大脑能量的重要性和可能机制。这些发现使我们假设，由于神经代谢的紧密耦合，脑氧化代谢应该是静息和激活脑的主要能量来源，然而，其能力可能是有限的，其大部分用于静息时的内在脑活动;因此，在任务诱发的CMRO 2变化和基线CMRO 2之间存在强相关性，以及能量补偿机构，用于在大脑激活期间以最佳功效利用大脑能量。通过使用基于17 O的CMRO 2成像方法结合其他已建立的方法（包括电生理记录），通过四个可检验的假设和四个特定目标，在猫脑中检查这一中心假设。这项研究将（i）强调大脑氧化代谢在基线和激活大脑状态的重要性;（ii）阐明与神经元活动和大脑功能相关的大脑生物能量学机制;（iii）为现代神经影像技术提供神经生理学基础。与公共卫生的相关性：本研究为探讨脑氧化代谢异常对脑功能障碍的影响提供了新的思路。基于17 O的CMRO 2成像模式的成功开发将进一步增强MR技术在神经科学发现和潜在的脑部疾病诊断中的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Modern neuroimaging such as fMRI and PET has opened up enormously exciting frontiers for studying brain function and human behavior. Understanding the relation between the imaging signals and the underlying brain physiology has become increasingly important and urgent. Although tremendous insights about neurovascular coupling have been gained, it is still elusive of the quantitative relation between brain metabolic energy and neuronal activity (i.e., neurometabolic coupling). Particularly important and intensely debated question is how much increases of cerebral metabolic rate of oxygen (CMRO2) are needed, or can be provided by brain for supporting task-evoked neuronal activity. The major challenge in this regard is the lack of a fast, noninvasive and quantitative method able to directly image absolute CMRO2 at both basal and activated brain states. The high-field 17O MRS imaging (MRSI) approach for imaging CMRO2 which has been successfully developed by us over the first funding cycle could overcome this hurdle. This innovative and unique approach offers a golden opportunity for studying the neurometabolic coupling and its impact on brain function. A large body of our preliminary results has not only demonstrated the feasibility, reliability and applicability of this 17O-based CMRO2 imaging approach, but also provided crucial evidence showing the importance and possible mechanism of cerebral oxidative metabolism for supporting brain energy at rest and during activation. These findings lead us to hypothesize that cerebral oxidative metabolism should be the major energy source for both resting and activated brain due to the tight neurometabolic coupling; however, its capacity might be limited which in large is used for intrinsic brain activity at rest; thus, there exist a strong correlation between task-evoked CMRO2 change and baseline CMRO2, and an energy compensation mechanism for utilizing brain energy during brain activation with optimal efficacy. This central hypothesis will be examined in the cat brain through four testable hypotheses and four specific aims by using 17O-based CMRO2 imaging approach combined with other established approaches including electrophysiology recording. This research will (i) highlight the importance of cerebral oxidative metabolism at both baseline and activated brain states; (ii) elucidate the mechanism of cerebral bioenergetics associated with neuronal activity and brain function; and (iii) provide the neurophysiology basis for modern neuroimaging techniques. Relevance to public health: This research could provide new insights about crucial impact of cerebral oxidative metabolism on the brain disorders and dysfunctions associated with oxidative metabolism abnormality. The success in developing the 17O-based CMRO2 imaging modality will further enhance the ability of MR technology in neuroscience discovery and potentially in diagnosis of brain diseases.