Assessment of cerebral metabolism in vivo by 17-Oxygen magnetic resonance imaging

描述(由申请人提供)： 尽管氧气消耗在神经系统疾病和功能研究中很重要，但目前还没有一种体内方法来绘制大脑氧气消耗代谢率的地图，这种方法结合了安全性和高时间和空间分辨率。例如，在决定用潜在危险的溶栓剂治疗中风期间的缺血组织时，还不知道可以挽救多少组织。受到威胁，但具有潜在生存能力的组织，血液流动恢复，维持了一些氧气消耗。因此，测量缺血区耗氧量的能力将为临床医生提供有关患者可能从治疗中获得多少好处的信息。氧耗重要性的另一个例子是阿尔茨海默病(AD)，众所周知，由于线粒体缺乏，氧代谢受到阻碍，但目前还没有临床可用的方法来测量AD患者的这些变化。一种测量耗氧量的技术可能对痴呆症患者具有诊断和预后价值，并有助于跟踪新出现的AD疗法的疗效。这一建议是基于氧的稳定、无毒、自然产生和核磁共振(核磁共振)活性形式：17O。由于17O_2气体是核磁共振不可见的，其代谢产物H_2170水是核磁共振可见的，17O可以作为一种非侵入性和非放射性的核磁共振成像代谢示踪剂。在间接检测方法中，由于自旋-自旋耦合，含17O的水以浓度依赖的方式缩短了质子的局部T1Rho和T2。基于T1 RHP的方法允许1H-17O相互作用的去耦合，这将在现有的临床扫描仪上实现，提供精确的局部H217O浓度而没有伪影。在这项提议中，将开发一种用于示踪剂递送的新型精确递送系统。通过将其与新兴的磁共振脉冲序列和体内非侵入性测量示踪剂动脉输入的定量方法配对，将在大型动物模型中生成氧代谢图。我们希望这项研究的完成将促进中风和AD的17O成像的临床试验。这项研究对公共卫生的影响是，它将提高医生对神经系统疾病的诊断和治疗做出决定的能力。特别是，可以获得新的信息来指导中风和阿尔茨海默病的治疗。

DESCRIPTION (provided by applicant): There is no in vivo method for mapping the cerebral metabolic rate of oxygen consumption that combines safety with high temporal and spatial resolution, despite the importance of oxygen consumption in neurological disease and functional studies. For example, in the decision to treat ischemic tissue during stroke with potentially dangerous thrombolytic agents, it is not known how much tissue it is possible to save. Threatened, yet potentially viable tissue with restored blood flow maintains some oxygen consumption. Therefore, the ability to measure oxygen consumption in the ischemic area would give clinicians information about how much possible benefit a patient may receive with therapy. Another example of the importance of oxygen consumption is in Alzheimer's Disease (AD), where it is known that oxygen metabolism is hampered due to mitochondrial deficiencies, yet there is no clinically usable method for measuring these changes in AD patients. A technique that measures oxygen consumption could be of diagnostic and prognostic value to patients with dementia, and help track the efficacy of emerging therapies for AD. This proposal is based on a stable, non-toxic, naturally-occurring, and nuclear magnetic resonance (NMR) active form of oxygen: 17O. Because 17O2 gas is NMR invisible and its metabolic product H2170 water is NMR visible, 17O can be used as a non-invasive and non-radioactive metabolic tracer for magnetic resonance imaging (MRI). In the indirect detection method, water containing 17O shortens the local T1Rho and T2 of protons in a concentration dependent manner due to spin-spin coupling. The T1 Rhp based methods allow for decoupling of the 1H-17O interaction that will provide precise local H217O concentrations without artifacts, implemented on existing clinical scanners. In this proposal, a novel precision delivery system for tracer delivery will be developed. By pairing this with emerging magnetic resonance pulse sequences and quantitative in vivo methods for non-invasively measuring the arterial input of the tracer, maps of oxygen metabolism will be generated in a large animal model. Our hope is that the completion of this research will spur clinical trials for 17O imaging of stroke and AD. The public health impact of this research is that it will improve the ability of physicians to make decisions about the diagnosis and treatment of diseases of the nervous system. In particular, new information could be gained to guide the treatment of stroke and Alzheimer's Disease.