A new ultra-low field in-vivo EPR technology for biomedical applications

用于生物医学应用的新型超低场体内 EPR 技术

• 批准号: 7762887
• 负责人: Inseob Hahn
• 金额: $ 19.63万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762887
• 关键词: Algae; Alzheimer' s Disease; Arts; Biomedical Technology; Caliber; Cardiology; Chemicals; Chlorella; Clinical; Detection; Devices; Electron Spin Resonance Spectroscopy; Electrons; Exercise; Foundations; Free Radicals; Frequencies; Generations; Goals; Heating; Human; Human Volunteers; Human body; Hybrids; Hyperbaric Oxygen; In Situ; Inorganic Sulfates; Ionizing radiation; Iron; Laboratories; Lead; Life; Light; Magnetism; Measurement; Measures; Methods; Mind; Modeling; Neurodegenerative Disorders; Neurology; Neurosciences; Nitric Oxide; Operating System; Oxidation-Reduction; Oxygen; Parkinson Disease; Penetration; Performance; Photosynthesis; Physiologic pulse; Play; Poisoning; Premature Infant; Radiation-Induced Cancer; Relaxation; Resolution; Role; Safety; Sampling; Scheme; Shapes; Signal Transduction; Site; Spectrometry; Spectrum Analysis; Spin Labels; Squid; Suspension substance; Suspensions; System; Techniques; Technology; Temperature; Testing; Toxicology; Ultraviolet Rays; United States National Institutes of Health; Unspecified or Sulfate Ion Sulfates; Work; absorption; base; biological systems; cost; cost effective; cryogenics; design; human disease; human study; human subject; improved; in vivo; instrument; magnetic field; microwave electromagnetic radiation; novel; oncology; operation; oxygen toxicity; prevent; public health relevance; research study; sensor; superconducting quantum interference device; technology development

DESCRIPTION (provided by applicant): The most successful uses of in vivo EPR have been non-invasive measurement of oxygen, nitric oxide, bioradicals, pH and redox state, with applications in oncology, cardiology, neuroscience and toxicology. These studies have been performed only in small size subjects due to fundamental limitations associated with the traditional high-frequency detection scheme. Current generation EPR systems typically use GHz or higher frequencies (L-, X-, Q- band) to achieve the required resolution. There are several key factors, which make in vivo EPR methods of human body at high frequencies extremely difficult, the principal ones being limits on the size and shape of the systems that can be measured and safety issues related to the absorption of high-level RF by biological systems. We will develop a new ultra-low field in vivo EPR spectrometer system that is safe for use in humans and has high sensitivity and good penetration depth. The new device will overcome the limitations associated with conventional EPR at high frequencies yet still achieve 100 to 1000 fold improved SNR over existing technology. We will achieve this goal by employing two state- of-the-art technologies developed in our lab: (1) a new microwave superconducting quantum interference device (MSQUID) (2) a cryogen-free, superconducting gradiometer system. Operation at 5MHz with a low power RF excitation will completely eliminate the problems associated with finite penetration depth and sample-heating. Our aims are: 1A) Demonstrate ?M-level EPR signal detection (both CW and pulse methods) using paramagnetic samples (e.g. spin probes) at room temperature using cryogenic detection with the new hybrid SQUID readout system. 1B) Demonstrate the NMR signal detection using the same detection system, with hybrid NMR/EPR spectroscopy systems in mind. 2) Use a cryogen-free cooling system with a large field-of-view detection coil to demonstrate EPR spectroscopy performance, using parameters suitable for the human study. 3) Demonstrate detection and measurement of electron paramagnetic resonance in biological systems at physiologically relevant concentrations. 3A. Using living suspensions of Chlorella pyroidenosa, we will attempt to detect the expected electron spin resonance under dark conditions, and to detect and quantify the ESR increase that occurs during photosynthesis. These technical aims form the foundations for the application of the advanced technology to human use. With the long term goal of a clinical device, we will also perform limited human testing. Our aim3B is to perform in vivo human experiments to detect increased free radical concentration during intense exercise. Our ultimate objective is to create a device for human in vivo biomedical EPR that is practical from the perspectives of safety, cost, siting and complexity, without compromising sensitivity and signal quality. PUBLIC HEALTH RELEVANCE (provided by applicant): Free radicals play a major role in human diseases such as iron sulfate poisoning, ionizing radiation, oxygen toxicity in premature infants treated with hyperbaric oxygen, ultraviolet radiation-induced cancer and very likely in Parkinson's, Alzheimer's and other neurodegenerative disorders. Electron paramagnetic resonance (EPR) is a non-invasive spectroscopic technique to detect and measure free radicals in chemical and biological system that has been applied in- vivo EPR to measure oxygen, nitric oxide, bioradicals, pH and redox state, with applications in oncology, cardiology, neurology and toxicology. To date, these studies have been performed only in small size subjects due to fundamental technical and safety limits of the conventional high-frequency detection scheme. We propose here to develop a novel ultra low-frequency EPR approach using a state-of-the-art magnetic flux sensor to enable safe, cost- effective and practical in vivo EPR humans, with an instrument ultimately capable of simultaneous NMR measurement.

描述（由申请人提供）：体内EPR的最成功用途是对氧气，一氧化氮，生物自由基，pH和氧化还原状态的无创测量，以及肿瘤学，心脏病学，神经科学和毒理学的应用。由于与传统的高频检测方案相关的基本限制，这些研究仅在小规模受试者中进行。当前一代EPR系统通常使用GHz或更高频率（L-，X-，Q-频段）来实现所需的分辨率。有几个关键因素，它们使人体的体内EPR方法非常困难，主要因素是可以测量的系统的大小和形状的限制，并且与高级RF的吸收有关的安全问题通过生物系统。我们将在体内EPR光谱仪系统中开发一个新的超低场，该领域可安全地用于人类，并且具有高灵敏度和良好的穿透深度。新设备将在高频上克服与常规EPR相关的局限性，但仍超过了现有技术的100到1000倍的SNR。我们将通过在实验室中采用两种状态技术来实现这一目标：（1）一种新的微波超导量子干扰装置（MSQUID）（2）无低温，超导层次计。低功率RF激发在5MHz的操作将完全消除与有限穿透深度和样品加热相关的问题。我们的目标是：1A）使用新混合型鱿鱼读数系统使用低温检测在室温下使用顺磁样品（例如自旋探针）在室温下使用顺磁样品（例如自旋探针）演示？M级EPR信号检测（CW和脉冲方法）。 1B）使用相同的检测系统展示NMR信号检测，并考虑了混合NMR/EPR光谱系统。 2）使用适合人类研究的参数，使用具有大量视野检测线圈的无低温冷却系统来证明EPR光谱性能。 3）证明在生理相关浓度下生物系统中电子顺磁共振的检测和测量。 3a。使用甲状腺小球藻的活悬浮液，我们将尝试在黑暗条件下检测预期的电子自旋共振，并检测和量化光合作用期间发生的ESR增加。这些技术目标构成了将先进技术应用于人类使用的基础。有了临床装置的长期目标，我们还将执行有限的人类测试。我们的AIM3B是进行体内人体实验，以检测强烈运动过程中自由基的增加。我们的最终目标是为人体生物医学EPR创建一种设备，从安全性，成本，选址和复杂性的角度来看，它在不损害灵敏度和信号质量的情况下是实用的。 公共卫生相关性（由申请人提供）：自由基在人类疾病中起着重要作用，例如硫酸铁中毒，电离辐射，用高压氧治疗的早产婴儿中的氧毒性，紫外线辐射诱发的癌症以及在帕金森氏症，阿尔茨海默氏症和阿尔茨海默氏症的癌症中很可能其他神经退行性疾病。电子顺磁共振（EPR）是一种非侵入性光谱技术，用于检测和测量化学和生物系统中的自由基，已应用于In-Vivo EPR来测量氧气，一氧化氮，生物自由基，生物自由基，pH和pH状态，并在肿瘤学中适用于肿瘤学中。 ，心脏病学，神经学和毒理学。迄今为止，由于常规高频检测方案的基本技术和安全限制，这些研究仅在小型受试者中进行。我们在这里建议使用最先进的磁通传感器开发一种新型的超低频EPR方法，以实现安全，成本效益和实用的体内EPR人体，并最终能够同时进行NMR测量。