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

17-氧磁共振成像评估体内脑代谢

• 批准号: 7409321
• 负责人: Eric Albert Mellon
• 金额: $ 3.01万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-04-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409321
• 关键词: Alzheimer' s Disease; Animal Model; Animals; Area; Arteries; Blood; Blood flow; Blood specimen; Bolus Infusion; Brain; Breathing; Cardiac; Cell Respiration; Cerebrum; Clinical; Clinical Trials; Cognitive; Consumption; Coupling; Decision Making; Degenerative Disorder; Dementia; Detection; Development; Diagnosis; Diagnostic; Disease; Family suidae; Fibrinolytic Agents; Future; Gases; Goals; Gold; Helium; Human; Human Volunteers; Image; Imaging Techniques; Invasive; Investigation; Kinetics; Lung; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Metabolic; Metabolism; Methods; Mitochondria; Modeling; Molecular; Morphologic artifacts; Neuraxis; Neurodegenerative Disorders; Noise; Nuclear Magnetic Resonance; Organ; Organism; Oxidative Phosphorylation; Oxygen; Oxygen Consumption; Oxygen Isotopes; Pathologic; Patients; Physicians; Physiologic pulse; Physiology; Positron-Emission Tomography; Process; Protocols documentation; Protons; Public Health; Pulse taking; Radioactive; Radioactive Tracers; Rate; Research; Resolution; Safety; Schizophrenia; Sensory; Signal Transduction; Solutions; Standards of Weights and Measures; Stroke; Sus scrofa; System; Techniques; Technology; Testing; Thinking; Tissues; Tracer; Validation; Water; awake; base; cost; design; human study; human subject; improved; in vivo; nervous system disorder; novel; post stroke; prognostic; research study; respiratory; tumor

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.

描述（由申请人提供）： 尽管在神经系统疾病和功能研究中含氧的重要性，但没有体内方法可以绘制氧气消耗的脑代谢率与高时间和空间分辨率相结合的脑代谢率。例如，在用潜在危险的溶栓剂治疗中风期间治疗缺血组织时，尚不知道可以节省多少组织。威胁性但潜在的有可能可恢复的血流的组织可保持一定的氧气消耗。因此，测量缺血区域中消耗的氧气的能力将为临床医生提供有关患者可以通过治疗获得多少受益的信息。氧气消耗重要性的另一个例子是阿尔茨海默氏病（AD），众所周知，由于线粒体缺陷，氧代谢受到了阻碍，但没有临床上可用的方法来测量AD患者的这些变化。一种测量氧气消耗的技术可能对痴呆症患者具有诊断性和预后价值，并有助于跟踪新兴疗法对AD的疗效。该提案基于稳定，无毒，自然发生和核磁共振（NMR）的活性形式的氧气：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，含有17O的水以浓度依赖于自旋旋转耦合而以浓度依赖性的质子缩短局部T1RHO和T2。基于T1 RHP的方法允许解耦1H-17O相互作用，该相互作用将在现有的临床扫描仪上实现精确的局部H217O浓度，而无需伪影。在此提案中，将开发出一种新颖的精确输送系统。通过将其与新兴的磁共振脉冲序列和非侵入性测量示踪剂的动脉输入的定量方法配对，将在大型动物模型中产生氧代谢的图。我们的希望是，这项研究的完成将刺激临床试验的17O中风和AD成像。这项研究的公共卫生影响是，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氏病的治疗。