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: (provided by applicant): 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.

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
2P41EB002034-14A1
Application #
8550946
Study Section
Special Emphasis Panel (ZEB1-OSR-E (M2))
Program Officer
Sastre, Antonio
Project Start
1999-09-30
Project End
2018-05-31
Budget Start
2013-07-15
Budget End
2014-05-31
Support Year
14
Fiscal Year
2013
Total Cost
$1,376,979
Indirect Cost
$317,145
Name
University of Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Epel, Boris; Sundramoorthy, Subramanian V; Krzykawska-Serda, Martyna et al. (2017) Imaging thiol redox status in murine tumors in vivo with rapid-scan electron paramagnetic resonance. J Magn Reson 276:31-36
Kuzhelev, Andrey A; Tormyshev, Victor M; Rogozhnikova, Olga Yu et al. (2017) Triarylmethyl Radicals: EPR Study of 13C Hyperfine Coupling Constants. Z Phys Chem (N F) 231:777-794
Shi, Yilin; Quine, Richard W; Rinard, George A et al. (2017) Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency. Z Phys Chem (N F) 231:923-937
Epel, Boris; Maggio, Matt; Pelizzari, Charles et al. (2017) Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization. Adv Exp Med Biol 977:287-296
Krzykawska-Serda, Martyna; Miller, Richard C; Elas, Martyna et al. (2017) Correlation Between Hypoxia Proteins and EPR-Detected Hypoxia in Tumors. Adv Exp Med Biol 977:319-325
Li, Yudu; Lam, Fan; Clifford, Bryan et al. (2017) A Subspace Approach to Spectral Quantification for MR Spectroscopic Imaging. IEEE Trans Biomed Eng 64:2486-2489
Shi, Yilin; Quine, Richard W; Rinard, George A et al. (2017) Triarylmethyl Radical OX063d24 Oximetry: Electron Spin Relaxation at 250 MHz and RF Frequency Dependence of Relaxation and Signal-to-Noise. Adv Exp Med Biol 977:327-334
Sundramoorthy, Subramanian V; Epel, Boris; Halpern, Howard J (2017) A Pulse EPR 25 mT magnetometer with 10ppm resolution. Appl Magn Reson 48:805-811
Nakagawa, Kouichi; Epel, Boris (2017) Investigating the Distribution of Stable Paramagnetic Species in an Apple Seed Using X-Band EPR and EPR Imaging. J Oleo Sci 66:315-319
Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas et al. (2017) Rapid-scan EPR imaging. J Magn Reson 280:140-148

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