STUDY OF BRAIN OXIDATIVE METABOLISM BY 17-0 IMAGING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 现代神经成像，如功能磁共振成像和正电子发射计算机断层扫描，为研究大脑功能和人类行为开辟了非常令人兴奋的前沿。了解成像信号与脑生理基础之间的关系变得越来越重要和迫切。虽然关于神经血管偶联的研究已经取得了很大的进展，但对于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)仍然难以捉摸。尤其重要和争论激烈的问题是，大脑需要增加多少脑氧代谢率(CMRO2)，或者大脑可以提供多少来支持任务诱发的神经元活动。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，能够在基础和激活的大脑状态下直接成像绝对的CMRO2。我们在第一个资助周期中成功开发的用于CMRO2成像的高场17O MRS成像(MRSI)方法可以克服这个障碍。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黄金机会。我们的大量初步结果不仅证明了这种基于17O的CMRO2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，显示了大脑氧化代谢在支持静息和激活期间大脑能量的重要性和可能的机制。这些发现导致我们假设，由于紧密的神经代谢耦合，大脑氧化代谢应该是休息和激活大脑的主要能量来源；然而，它的能力可能是有限的，主要用于静止时的内在大脑活动；因此，任务诱发的CMRO2变化与基线CMRO2之间存在强烈的相关性，以及在大脑激活过程中以最佳效果利用大脑能量的能量补偿机制。这一中心假说将通过四个可测试的假说和四个特定的目标在猫脑中进行检验，方法是使用基于17O的CMRO2成像方法，并结合其他已建立的方法，包括电生理记录。这项研究将(I)强调大脑氧化代谢在基线和激活脑状态下的重要性；(Ii)阐明脑生物能量学与神经元活动和脑功能相关的机制；以及(Iii)为现代神经成像技术提供神经生理学基础。与公众健康相关：这项研究可以为大脑氧化代谢对与氧化代谢异常相关的大脑紊乱和功能障碍的关键影响提供新的见解。开发基于17O的CMRO2成像模式的成功将进一步增强MR技术在神经科学发现和潜在诊断大脑疾病方面的能力。

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.