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

描述（由申请人提供）： 尽管耗氧量在神经系统疾病和功能研究中很重要，但没有将安全性与高时间和空间分辨率相结合的体内方法来绘制耗氧量的脑代谢率。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，不知道有多少组织可能被保存。受威胁的，但可能有活力的组织与恢复血流保持一定的氧气消耗。因此，测量缺血区域的耗氧量的能力将为临床医生提供关于患者可能从治疗中获得多少益处的信息。氧消耗的重要性的另一个例子是在阿尔茨海默病（AD）中，已知氧代谢由于线粒体缺陷而受阻，但没有临床上可用的方法来测量AD患者中的这些变化。一种测量耗氧量的技术可能对痴呆患者具有诊断和预后价值，并有助于跟踪AD新兴疗法的疗效。该提议基于一种稳定、无毒、天然存在的核磁共振（NMR）活性形式的氧：17 O。由于17 O2气体是NMR不可见的，而其代谢产物H2170水是NMR可见的，因此17 O可以用作磁共振成像（MRI）的非侵入性和非放射性代谢示踪剂。在间接检测方法中，由于自旋-自旋耦合，含有17 O的水以浓度依赖的方式缩短质子的局部T1 Rho和T2。基于T1 Rhp的方法允许1H-17 O相互作用的解耦，这将提供精确的局部H217 O浓度而没有伪影，在现有的临床扫描仪上实现。在这项建议中，将开发一种用于示踪剂投放的新型精确投放系统。通过将其与新兴的磁共振脉冲序列和用于非侵入性测量示踪剂的动脉输入的定量体内方法配对，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刺激中风和AD的17 O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.