MITOCHONDRIAL REDOX IMAGING OF BIOLOGICAL TISSUES

生物组织的线粒体氧化还原成像

• 批准号: 8361949
• 负责人: LIN LI
• 金额: $ 1.54万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361949
• 关键词: Biological; Calibration; Cardiovascular Diseases; Computer software; Development; Diabetes Mellitus; Disease; Flavoproteins; Fluorescence; Funding; Generations; Grant; Image; Imaging technology; Magnetic Resonance; Malignant Neoplasms; Metabolic; Mitochondria; Molecular Abnormality; NADH; National Center for Research Resources; Neurodegenerative Disorders; Nicotinamide adenine dinucleotide; Oxidation-Reduction; Play; Principal Investigator; Procedures; Reactive Oxygen Species; Relative (related person); Research; Research Infrastructure; Resolution; Resources; Scanning; Signal Transduction; Source; Time; Tissues; United States National Institutes of Health; base; cold temperature; cost; fluorescence imaging; imaging modality; in vivo; instrument; optical imaging

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The development of cutting edge technologies for imaging the mitochondrial metabolic function including the redox state of biological tissues are in great need, since mitochondria and its functional/genetic abnormalities have been connected to a number of diseases including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imaging or "redox scanning" has been developed since about 30 years ago to image the in vivo mitochondrial redox states of tissues on the basis of the redox ratios (Fp/NADH or Fp/(NADH+Fp)). A CCD-based redox imager has also been built to acquire images much faster with higher spatial resolution (~10 pm). However, redox ratio is based on the ratio of the relative intensities of the fluorescence signals of NADH and Fp, which usually depend on instrument settings such as filters and lamp conditions. In this project we aim to develop a calibration procedure to quantify NADH and Fp signals so that redox images obtained at different time or with different settings can be compared. We also aim to upgrade the hardware and software of the old redox scanner to a new pc-control unit that will acquire redox images faster with higher SNR and signal dynamic ranges. We also aim to develop tissue imaging methods for reactive oxygen species, which are connected to mitochondrial redox state and also implicated to play key role in the generation and progression of many diseases.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 线粒体代谢功能成像尖端技术的发展 包括生物组织的氧化还原状态是​​非常需要的，因为线粒体及其 功能/遗传异常与许多疾病有关，包括癌症、 糖尿病、心血管疾病和神经退行性疾病。低温 NADH/Fp （还原型烟酰胺腺嘌呤二核苷酸/氧化黄素蛋白）荧光成像或 “氧化还原扫描”大约在 30 年前就已被开发出来，用于对体内进行成像 基于氧化还原比（Fp/NADH 或 Fp/(NADH+Fp)）的组织线粒体氧化还原状态。 还构建了基于 CCD 的氧化还原成像仪，能够以更高的空间速度更快地获取图像。 决议（~晚上 10 点）。然而，氧化还原比是基于相对强度的比率 NADH 和 Fp 的荧光信号，通常取决于仪器设置，例如 过滤器和灯的条件。在这个项目中，我们的目标是开发一个校准程序来量化 NADH 和 Fp 信号，以便在不同时间或使用不同设置获得氧化还原图像 可以比较。我们还致力于升级旧氧化还原扫描仪的硬件和软件 到一个新的电脑控制单元，将更快地获取氧化还原图像，具有更高的信噪比和信号 动态范围。 我们还致力于开发活性氧的组织成像方法， 它们与线粒体氧化还原状态有关，并且在 许多疾病的产生和发展。