Discrete Wavelength Frequency Domain Near Infrared Spectroscopy for Non-Invasive Measurement of Cytochrome Oxidation State

离散波长频域近红外光谱法用于细胞色素氧化态的非侵入性测量

• 批准号: 10272895
• 负责人: Robert H Thiele
• 金额: $ 57.61万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2024-09-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10272895
• 关键词: Beer; Benchmarking; Biological; Blood; Brain; Cause of Death; Cell Death; Cell Hypoxia; Cells; Cerebral Ischemia; Cessation of life; Critical Illness; Cyanides; Cytochromes; Data Set; Devices; Disease; Electron Transport; Engineering; Environment; Extinction (Psychology); Frequencies; Functional disorder; Goals; HGF gene; Halogens; Heme aa3 Cytochrome Oxidase; Hemoglobin; Hemorrhage; Hemorrhagic Shock; Human; Hypoxia; Infrared Rays; Injections; Ischemia; Knowledge; Laboratories; Lasers; Laws; Light; Lipids; Liquid substance; Literature; Mammals; Measurement; Measures; Mitochondria; Molecular; Myocardial Ischemia; Near-Infrared Spectroscopy; Optics; Organ; Organelles; Outcome; Oxidative Phosphorylation; Oxides; Oxygen; Patient Monitoring; Performance; Photons; Play; Prevention; Process; Protocols documentation; Publishing; Rattus; Research; Role; Scientist; Sepsis; Silicon; Source; Spectrum Analysis; Stroke; Surrogate Markers; System; Techniques; Technology; Testing; Tissues; Trauma; Tube; Work; Yeasts; absorption; base; chromophore; density; detector; improved; in silico; insight; instrument; novel; oxidation; photomultiplier; photon-counting detector; prevent; quantum; simulation; temporal measurement; tissue phantom

PROJECT SUMMARY / ABSTRACT (DESCRIPTION) Four of the top 10 worldwide causes of death are related to oxygen supply:demand mismatching,(2) and two involve infectious processes(2) which are known to impact the mitochondria,(27) the oxygen-producing organelles which generate the majority of ATP in mammals. Despite the essential function of oxidative phosphorylation (OXPHOS) in human survival,(28) and the disruption of OXPHOS that occurs in a variety of disease states, our understanding of the exact process of hypoxic cell death remains incompletely understood.(28-30) This proposal’s objective is to construct and experimentally validate a frequency-domain near infrared spectroscopy (NIRS) instrument capable of measuring absolute concentrations of oxidized and reduced forms of cytochrome aa3, the terminal component of the electron transport chain (ETC). Our long term goal is to develop a patient monitor capable of detecting organ ischemia at the level of the mitochondria (ETC dysfunction) to facilitate prevention and treatment of leading causes of death. Our central hypothesis is that combination of emerging advances in engineering, in particular the use of advanced photon detectors (e.g. silicon photomultipliers [SiPM]) as well as novel combinations of near infrared radiation (NIR) wavelengths, will allow for accurate measurement of CytOX. We will test our central hypothesis and achieve our objective via the following specific aims: Specific Aim 1: Select Wavelength Number and Frequency. Using in silico simulation, we will test all possible combinations of commercially available wavelengths of lasers that can be modulated at 100 MHz to determine the combinations which offer the most attractive tradeoff between accuracy (CytOX validated against broadband) and simplicity (least number of wavelengths), using a pre-existing dataset; Specific Aim 2: Optimize Photon Detection. In a laboratory environment, we will test combinations of near infrared laser light and extended range photomultiplier tubes to identify a combination suitable for frequency domain spectroscopy measurement of CytOX (the oxidation state of cytochrome aa3); Specific Aim 3: Construct and Test a Functioning FD-NIRS Device to Measure CytOX. We will construct and test a frequency domain instrument capable of measuring absolute concentrations of hemoglobin (oxygenated, de-oxygenated) and cytochrome aa3 (oxidized, reduced) in a quasi-biological tissue phantom.

项目摘要/摘要（描述） 全球十大死亡原因中，有四个与氧气供应有关：需求不匹配，(2) 和两个 涉及感染过程（2），已知会影响线粒体，（27）产氧细胞 尽管具有氧化功能，但在哺乳动物中产生大部分 ATP 的细胞器。 磷酸化 (OXPHOS) 对人类生存的影响，(28) 以及 OXPHOS 的破坏发生在多种疾病中 在疾病状态下，我们对缺氧细胞死亡的确切过程的理解仍然不完全 理解。(28-30) 该提案的目标是构建并通过实验验证频域 近红外光谱 (NIRS) 仪器能够测量氧化和氧化的绝对浓度 细胞色素 aa3 的还原形式，电子传递链 (ETC) 的末端成分。 长期目标是开发一种能够在线粒体水平上检测器官缺血的患者监视器 （ETC 功能障碍）促进主要死亡原因的预防和治疗 我们的中心假设是。 工程领域新兴进步的结合，特别是先进光子探测器（例如 硅光电倍增管 [SiPM]）以及近红外辐射 (NIR) 波长的新颖组合，将 允许准确测量 CytOX。我们将测试我们的中心假设并通过以下方式实现我们的目标。 具体目标如下： 具体目标 1：选择波长数和频率在计算机模拟中使用。 我们将测试商用激光器波长的所有可能组合，这些波长可以在 100 MHz 以确定提供准确度之间最具吸引力的权衡的组合 (CytOX 使用预先存在的数据集，针对宽带进行验证）和简单性（最少的波长数）； 具体目标 2：优化光子检测 在实验室环境中，我们将测试近邻的组合。 红外激光和增程光电倍增管，以确定适合频率的组合 CytOX（细胞色素 aa3 的氧化态）的域光谱测量；具体目标 3：构建 并测试功能正常的 FD-NIRS 设备来测量 CytOX 我们将构建并测试频域。 能够测量血红蛋白（含氧、脱氧）绝对浓度的仪器 准生物组织模型中的细胞色素 aa3（氧化、还原）。