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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 用于成像线粒体代谢功能的尖端技术的开发 包括生物组织的氧化还原状态非常需要，因为线粒体及其 功能/遗传异常已与多种疾病有关，包括癌症， 糖尿病，心血管疾病和神经退行性疾病。低温NADH/FP （减少烟酰胺腺嘌呤二核苷酸/氧化黄蛋白）荧光成像或 “氧化还原扫描”从大约30年前开始开发，以对体内产生图像 基于氧化还原比（FP/NADH或FP/（NADH+FP））组织的线粒体氧化还原状态。 还构建了基于CCD的氧化还原成像仪，以更快地获取图像的速度更高 分辨率（〜10 pm）。但是，氧化还原比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 过滤器和灯条件。在这个项目中，我们旨在制定校准程序来量化 NADH和FP信号，以便在不同时间或不同设置中获得的氧化还原图像 可以比较。我们还旨在升级旧的氧化还原扫描仪的硬件和软件 到一个新的PC控制单元，该单元将使用较高的SNR和信号更快地获取氧化还原图像 动态范围。 我们还旨在开发用于活性氧的组织成像方法， 与线粒体氧化还原状态相关的，也牵涉到在 许多疾病的产生和进展。