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

基本信息

  • 批准号:
    7762887
  • 负责人:
  • 金额:
    $ 19.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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 最成功的用途是无创测量氧气、一氧化氮、生物自由基、pH 值和氧化还原状态,并应用于肿瘤学、心脏病学、神经科学和毒理学。由于传统高频检测方案的基本限制,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。有几个关键因素使得高频人体体内 EPR 方法变得极其困难,其中主要因素是可测量系统的尺寸和形状的限制以及与生物系统吸收高水平射频相关的安全问题。我们将开发一种新型超低场活体EPR光谱仪系统,该系统可安全用于人体,并且具有高灵敏度和良好的穿透深度。新器件将克服与高频下传统 EPR 相关的限制,但仍能实现比现有技术提高 100 至 1000 倍的 SNR。我们将通过采用实验室开发的两项最先进的技术来实现这一目标:(1) 新型微波超导量子干涉装置 (MSQUID) (2) 无制冷剂超导梯度计系统。采用低功率射频激励在 5MHz 下运行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) 使用新型混合 SQUID 读出系统的低温检测,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(连续波和脉冲方法)。 1B) 使用相同的检测系统演示 NMR 信号检测,并考虑混合 NMR/EPR 光谱系统。 2) 使用带有大视场检测线圈的无制冷剂冷却系统来演示 EPR 光谱性能,并使用适合人体研究的参数。 3) 展示生物系统中生理相关浓度下电子顺磁共振的检测和测量。 3A。我们将利用活体焦化小球藻悬浮液,尝试检测黑暗条件下预期的电子自旋共振,并检测和量化光合作用过程中发生的 ESR 增加。这些技术目标构成了先进技术应用于人类的基础。为了实现临床设备的长期目标,我们还将进行有限的人体测试。我们的目标3B是进行体内人体实验,以检测剧烈运动期间自由基浓度的增加。我们的最终目标是创建一种用于人体体内生物医学 EPR 的设备,该设备从安全性、成本、选址和复杂性的角度来看都是实用的,同时又不影响灵敏度和信号质量。 公共健康相关性(由申请人提供):自由基在人类疾病中发挥着重要作用,例如硫酸铁中毒、电离辐射、高压氧治疗的早产儿的氧中毒、紫外线辐射诱发的癌症,并且很可能在帕金森病、阿尔茨海默病和其他神经退行性疾病中发挥作用。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,已应用于体内EPR测量氧、一氧化氮、生物自由基、pH和氧化还原状态,在肿瘤学、心脏病学、神经学和毒理学中得到应用。迄今为止,由于传统高频检测方案的基本技术和安全限制,这些研究仅在小规模受试者中进行。我们在此建议开发一种新型超低频 EPR 方法,使用最先进的磁通量传感器,以实现安全、经济高效且实用的人体体内 EPR,并最终使用能够同时进行 NMR 测量的仪器。

项目成果

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Inseob Hahn其他文献

Inseob Hahn的其他文献

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{{ truncateString('Inseob Hahn', 18)}}的其他基金

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:
    8279155
  • 财政年份:
    2010
  • 资助金额:
    $ 19.63万
  • 项目类别:
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:
    8137636
  • 财政年份:
    2010
  • 资助金额:
    $ 19.63万
  • 项目类别:
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