High resolution images of molecular oxygenation have been shown to provide crucial guides to the delivery and monitoring of cancer therapy in model systems. Stroke and myocardial infarction therapies may similarly benefit. EPR imaging (EPRl) of oxygen (EPROI) provides a unique combination of spatial resolution, oxygen resolution, time resolution and uniform sensitivity with depth in tissue. This Center focuses on the optimization of In Vivo EPR Oxygen Imaging anticipating human images. It is a consortium between the Universities of Chicago, Denver, Maryland, and the Novosibirsk Institute of Organic Chemistry, Russia. EPROI requires coordinated development of multidisciplinary technologies: instrumentation for spectroscopic imaging, spin probes to sample and report the tissue fluid environment and imaging strategies to optimally sample and analyze the image information obtained- The Center is built on this multidisciplinary effort from medical physicists, engineers, biologists, radiation oncologists, physical and organic chemists, statisticians and imaging mathematicians. In the past 5 years the Center: 1) implemented T1/R1 sensitive pulse sequences that free trityl based EPR oxygen images from confounding variations; 2) developed and made routine highly sensitive Electron Spin Echo pulse imaging as a Tl and T2 readout; 3) enhanced signal to noise ratio per unit time (SNR/t) of pulse imaging with novel technical methods; 4) developed methods for large object imaging; 5) applied novel nitroxide sensitive rapid scan imaging to animal systems; 6) made significant progress toward the development of unusually narrow line trityls; 7) synthesized novel very narrow line deuterated nitroxides for pH and thiol imaging. These achievements prepare the Center for the promise of its final funding cycle, work toward human application. Toward that end we propose the following Technology Research and Development Projects: 1) Higher SNR/t for enhanced spatial and p02 resolution EPROI; 2) Rapid EPROI acquisition - time resolved three dimensional oxygen image movies; 3) Enhanced registration of EPROI with multimodality imaging for better definition of tissue and tumor microenvironment; 4) Commercial small animal pulse oxygen and rapid scan imaging systems to accelerate pharmaceutical development and the development of a human imager prototype. The last aim fulfills the Center mission of commercial migration of the EPRl technology. We will work with Bruker BioSpin on a commercial small animal imaging system.

Public Health Relevance

This proposal will improve the sensitivity and accuracy of electron paramagnetic resonance imaging (EPRl) of oxygen (EPROI) in the tissues and tumors of living animals. Molecular oxygen availability determines resistance to radiation therapy and is a determinant of stroke, heart attack and peripheral vascular disease. We will work with Bruker BioSpin to develop an animal EPROI to accelerate development of anti-angiogenic drugs and to investigate radiation therapy dose painting in preclinical animal models.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZEB1-OSR-E (M2))
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Sastre, Antonio
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University of Chicago
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