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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000890-03
Application #
6776417
Study Section
Diagnostic Imaging Study Section (DMG)
Program Officer
Mclaughlin, Alan Charles
Project Start
2002-09-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$726,899
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Dhimitruka, Ilirian; Alzarie, Yasmin Alsayed; Hemann, Craig et al. (2016) Trityl radicals in perfluorocarbon emulsions as stable, sensitive, and biocompatible oximetry probes. Bioorg Med Chem Lett 26:5685-5688
Song, Yuguang; Liu, Yangping; Liu, Wenbo et al. (2014) Characterization of the Binding of the Finland Trityl Radical with Bovine Serum Albumin. RSC Adv 4:47649-47656
Johnson, David H; Ahmad, Rizwan; Liu, Yangping et al. (2014) Uniform spinning sampling gradient electron paramagnetic resonance imaging. Magn Reson Med 71:893-900
Johnson, David H; Ahmad, Rizwan; He, Guanglong et al. (2014) Compressed sensing of spatial electron paramagnetic resonance imaging. Magn Reson Med 72:893-901
Song, Yuguang; Liu, Yangping; Hemann, Craig et al. (2013) Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity. J Org Chem 78:1371-6
Liu, Yangping; Villamena, Frederick A; Rockenbauer, Antal et al. (2013) Structural factors controlling the spin-spin exchange coupling: EPR spectroscopic studies of highly asymmetric trityl-nitroxide biradicals. J Am Chem Soc 135:2350-6
Chen, Zhiyu; Reyes, Levy A; Johnson, David H et al. (2013) Fast gated EPR imaging of the beating heart: spatiotemporally resolved 3D imaging of free-radical distribution during the cardiac cycle. Magn Reson Med 69:594-601
Caia, George L; Efimova, Olga V; Velayutham, Murugesan et al. (2012) Organ specific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging. J Magn Reson 216:21-7
Liu, Yangping; Song, Yuguang; De Pascali, Francesco et al. (2012) Tetrathiatriarylmethyl radical with a single aromatic hydrogen as a highly sensitive and specific superoxide probe. Free Radic Biol Med 53:2081-2091
Sun, Ziqi; Li, Haihong; Petryakov, Sergey et al. (2012) In vivo proton electron double resonance imaging of mice with fast spin echo pulse sequence. J Magn Reson Imaging 35:471-5

Showing the most recent 10 out of 50 publications