In vivo imaging and spectroscopy of pH and thiols status

pH 和硫醇状态的体内成像和光谱

• 批准号: 6867370
• 负责人: Valery V Khramtsov
• 金额: $ 15.32万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867370
• 关键词: acidity /alkalinity; bioimaging /biomedical imaging; electron spin resonance spectroscopy; glutathione; heart imaging /visualization /scanning; ischemic preconditioning; laboratory rat; molecular probes; myocardial ischemia /hypoxia; nitrogen oxides; reperfusion; spectrometry; technology /technique development; thiols; tissue /cell culture; tissue /cell preparation

DESCRIPTION (provided by applicant): This proposal will provide new training and a significant shift in career direction for the P.I. from fields of fundamental physical and organic chemistry to applied biomedical imaging and spectroscopy. Studies will be performed at the OSU Biomedical Spectroscopy and Imaging Center, a unique training environment with emerging state-of-the art techniques and with additional learning opportunities in experimental physiology and cell biology that will ensure progress toward independence of the P.I. The overall experimental plan will develop new biomedical imaging and spectroscopy applications for a group of pH- and thiol (SH)-sensitive nitroxides, previously synthesized by the P.I. and colleagues. Current methods for spatial and temporal detection of pH and SH in living tissues and organisms either have significant limitations or do not exist. Therefore, these new approaches could represent a breakthrough in physiologic monitoring in a variety of settings. Experiments will focus on applications related to cardiac ischemia and ischemia-reperfusion injury. The specific aims are: (SA1) To critically evaluate existing and newly synthesized pH- and SH-sensitive nitroxides as functional probes for in vivo electron paramagnetic resonance (EPR) applications. Functional sensitivity, stability towards reduction in biological tissues and capacity for in vivo/cellular distribution will be studied. A series of new probes will also be tested which are specifically designed to enhance these probe attributes. (SA2) To develop functional EPR-based spectroscopy and imaging for the investigation of time and spatially-resolved pH and SH content in living tissues. Initial studies will optimize techniques for probe administration, maximization of spatial and intensity resolution and minimization of toxicity. The experiments are planned using these techniques to evaluate a new hypothesis: namely, that pH-induced changes in myocardial buffering capacity, developed during preconditioning, are important in functional protection of the heart during subsequent prolonged ischemia. Preliminary experiments demonstrate the potential importance of this relatively unknown mechanism. (SA3) To obtain the necessary tools and skills in imaging and in medical science to bridge the interface between physical chemistry, applied biomedical sciences and imaging technology. The success of this project may have a significant impact on the future of bioimaging applications to medicine.

描述（由申请人提供）： 该建议将为P.I.提供新的培训，并在职业方向上发生重大转变。从基本的物理和有机化学领域到应用生物医学成像和光谱法。研究将在OSU生物医学光谱和成像中心进行，这是一个独特的培训环境，具有新兴的最新技术，并在实验生理学和细胞生物学方面具有额外的学习机会，以确保P.I的独立性发展。总体实验计划将开发一组pH-和硫醇（SH）敏感的氮氧化物的新生物医学成像和光谱应用，该硝酸氧化物先前由P.I合成。和同事。当前在生物组织和生物中pH和SH的空间和时间检测的当前方法具有重大局限性或不存在。因此，这些新方法可以代表各种环境中生理监测的突破。实验将集中于与心脏缺血和缺血 - 再灌注损伤有关的应用。具体目的是：（SA1）批判性地评估现有和新合成的pH-和SH敏感性氮氧化物作为体内电子磁性共振（EPR）应用的功能探针。将研究功能敏感性，生物组织降低的稳定性以及体内/细胞分布的能力。还将测试一系列新的探针，这些探针是专门设计的，以增强这些探针属性。 （SA2）开发基于功能EPR的光谱和成像，以研究活组织中时间和空间分辨的pH和SH含量。初步研究将优化用于探测，空间和强度分辨率最大化以及毒性最小化的技术。该实验是使用这些技术来评估新假设的：即，在预处理期间开发的pH诱导的心肌缓冲能力变化对于随后延长的缺血期间对心脏的功能保护很重要。初步实验证明了这种相对未知机制的潜在重要性。 （SA3）获得成像和医学中必要的工具和技能，以弥合物理化学，应用生物医学科学和成像技术之间的界面。该项目的成功可能会对医学生物成像应用的未来产生重大影响。