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，但目前还没有一种体内方法可以将安全性与高时间和空间分辨率结合起来绘制脑耗氧代谢率。例如，在决定使用潜在危险的溶栓剂治疗中风期间的缺血组织时，尚不清楚可以挽救多少组织。受到威胁但具有恢复血流的潜在活力的组织会维持一定的耗氧量。因此，测量缺血区域耗氧量的能力将为临床医生提供有关患者通过治疗可能获得多少益处的信息。耗氧量重要性的另一个例子是阿尔茨海默病 (AD)，众所周知，由于线粒体缺陷，氧代谢受到阻碍，但临床上尚无可用的方法来测量 AD 患者的这些变化。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，并有助于追踪 AD 新兴疗法的疗效。该提议基于稳定、无毒、天然存在的核磁共振 (NMR) 活性氧形式：17O。由于 17O2 气体是 NMR 不可见的，其代谢产物 H2170 水是 NMR 可见的，因此 17O 可用作磁共振成像（MRI）的非侵入性、非放射性代谢示踪剂。在间接检测方法中，含有 17O 的水由于自旋-自旋耦合以浓度依赖性方式缩短质子的局部 T1Rho 和 T2。基于 T1 Rhp 的方法允许解耦 1H-17O 相互作用，这将提供精确的局部 H217O 浓度，没有伪影，可在现有临床扫描仪上实施。在该提案中，将开发一种用于示踪剂输送的新型精密输送系统。通过将其与新兴的磁共振脉冲序列和用于无创测量示踪剂动脉输入的定量体内方法相结合，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 成像临床试验。这项研究对公共健康的影响在于，它将提高医生诊断和治疗神经系统疾病的决策能力。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.