In Vivo EPR/NMR Co-Imaging of Free Radicals

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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.