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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB002034-15
Application #
8701126
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
2014-06-01
Budget End
2015-05-31
Support Year
15
Fiscal Year
2014
Total Cost
$1,167,203
Indirect Cost
$263,664
Name
University of Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Christodoulou, Anthony G; Redler, Gage; Clifford, Bryan et al. (2016) Fast dynamic electron paramagnetic resonance (EPR) oxygen imaging using low-rank tensors. J Magn Reson 270:176-82
Yang, Zhongyu; Bridges, Michael D; López, Carlos J et al. (2016) A triarylmethyl spin label for long-range distance measurement at physiological temperatures using T1 relaxation enhancement. J Magn Reson 269:50-4
Epel, Boris; Redler, Gage; Pelizzari, Charles et al. (2016) Approaching Oxygen-Guided Intensity-Modulated Radiation Therapy. Adv Exp Med Biol 876:185-93
Epel, Boris; Redler, Gage; Tormyshev, Victor et al. (2016) Towards Human Oxygen Images with Electron Paramagnetic Resonance Imaging. Adv Exp Med Biol 876:363-9
Tseytlin, Mark; Epel, Boris; Sundramoorthy, Subramanian et al. (2016) Decoupling of excitation and receive coils in pulsed magnetic resonance using sinusoidal magnetic field modulation. J Magn Reson 272:91-99
Trukhin, Dmitry V; Rogozhnikova, Olga Yu; Troitskaya, Tatiana I et al. (2016) Facile and High-Yielding Synthesis of TAM Biradicals and Monofunctional TAM Radicals. Synlett 27:893-899
Epel, Boris; Halpern, Howard J (2015) Comparison of pulse sequences for R1-based electron paramagnetic resonance oxygen imaging. J Magn Reson 254:56-61
Epel, Boris; Halpern, Howard J (2015) In Vivo pO2 Imaging of Tumors: Oxymetry with Very Low-Frequency Electron Paramagnetic Resonance. Methods Enzymol 564:501-27
Redler, Gage; Epel, Boris; Halpern, Howard J (2015) Maximally spaced projection sequencing in electron paramagnetic resonance imaging. Concepts Magn Reson Part B Magn Reson Eng 45:33-45

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