In Vivo EPR/NMR Co-Imaging of Free Radicals

描述（由申请人提供）： 氧自由基和一氧化氮是细胞功能和许多疾病过程的核心重要性损伤的关键介质，包括：心脏病发作;中风;败血性休克;癌症;和衰老。鉴于这种重要性，非常需要能够对自由基或疾病的动物模型进行体内测量和成像的方法。EPR成像是一种功能强大的技术，能够以亚毫米分辨率对自由基代谢、氧合和一氧化氮进行三维空间映射。该技术具有在活体动物中绘制顺磁物质的独特能力，然而，EPRI的实用性和能力受到以下事实的极大限制，即它不提供该图像数据在体内的解剖配准。我们最近已经证明，结合使用EPRI和质子MRI技术，可以实现精确的图像配准，并提供一个显着的协同作用的能力，以获得重要的生物医学信息。这些技术在单一仪器中的组合使用具有彻底改变生命系统中的自由基测量领域的潜力，提供高质量的解剖图像配准以及可从EPR和基于NMR的MRI获得的独特信息的相关性。因此，我们建议开发和优化一种独特的混合仪器，适用于EPRI和质子MRI。在该提案中，有一系列5个具体目标，提供了创建和优化这种新型多模式MRI仪器所需的关键开发步骤。这些措施包括：开发磁体、梯度、磁场控制和系统接口，优化EPR和NMR MRI; 11.开发窄带和固定频率的射频电桥，使活动物的EPR灵敏度最大化，并提供最小化运动或其他来源的噪音; 111.开发EPIUNMR MRI谐振器，用于具有自动调谐和自动耦合能力的体内生物医学应用的最大灵敏度和稳定性; IV.开发用于EPR和NMR MRI控制、图像采集、重建和分析的优化软件，提供快速图像数据收集以及解剖结构和自由基分布的共同映射。这些创新将导致开发一种新型的EPIUNMR MRI仪器，该仪器优化用于各种重要疾病动物模型中自由基，氧气和一氧化氮的体内测量和成像。

DESCRIPTION (provided by applicant): Oxygen free radicals and nitric oxide are critical mediators of cellular function and injury of central importance of many disease processes including: heart attack; stroke; septic shock; cancer; and aging. In view of this importance, there has been a great need for methods enabling in vivo measurement and imaging of free radicals or animal models of disease. EPR imaging is a powerful technique that enables three-dimensional spatial mapping of free radical metabolism, oxygenation, and nitric oxide with submillimeter resolution. This technology has the unique ability to map paramagnetic species in living animals, however, the utility and power of EPRI has been greatly limited by the fact that it does not provide an anatomic registration of this image data within the body. We have recently demonstrated that combined use of EPRI and proton MRI techniques can enable precise image registration and provide a marked synergy in the ability to obtain important biomedical information. Combined use of these techniques in a single instrument has the potential to revolutionize the field of free radical measurement in living systems, providing high quality anatomic image registration and correlation of the unique information obtainable from EPR and NMR based MRI. Therefore, we propose to develop and optimize a unique hybrid instrument suitable for both EPRI and proton MRI. In this proposal there are a series of 5 specific aims that provide the critical development steps necessary to create and optimize this new multimodal MRI instrument. These include: I. Development of a magnet, gradient, field control, and system interface optimized for EPR and NMR MRI; 11. Development of narrow band and fixed frequency RF bridges for maximum EPR sensitivity in living animals with provisions to minimize noise from motion or other sources; 111. Development of EPIUNMR MRI resonators for maximum sensitivity and stability for in vivo biomedical applications with automatic tuning and automatic coupling capability; IV. Development of optimized software for EPR and NMR MRI control, image acquisition, reconstruction and analysis, with provisions enabling rapid image data collection and co-mapping of anatomic structure and free radical distribution. These innovations will result in development of a new type of EPIUNMR MRI instrument optimized for in vivo measurement and imaging of free radicals, oxygen, and nitric oxide in a variety of important animal models of disease.