High resolution images of molecular oxygenation images can provide crucial guides to the delivery and monitoring of cancer therapy. EPR imaging (EPRI) of oxygen provides a unique combination of spatial resolution, oxygen resolution, and uniform sensitivity with depth in tissue. This Center focuses on the optimization of In Vivo EPRI oxygen imaging anticipating human images. It is a consortium between the Universities of Chicago, Maryland and Denver. Successful images require coordinated development of instrumentation to obtain the images, spin probes to sample and report the tissue fluid environment and imaging strategies to optimally sample and analyze the information obtained. The Center is built on multidisciplinary effort from engineers, biologists, radiation oncologists, medical physicists, physical and organic chemists, statisticians and imaging mathematicians. In the past 21/2 years the Center 1) validated EPRI oxygen images point by point, 2) developed co-registration of oxygen with anatomy and other physiology, 3) increased animal tumor size imaged, 4) produced the first electron spin echo oxygen image nearly an order of magnitude faster than continuous wave (CW) acquisition, 5) developed a source of narrow line trityl spin probe capable of bulk synthesis, 6) synthesized persistent intracellular nitroxides and 7) radically altered reconstruction of images from projections allowing partial projections in even dimensions. These achievements directly improve spatial, oxygenation and/or temporal image resolution. Physiologically relevant resolution goals mandates improvement in resolution of EPRI oxygen images for small animals. This improvement will be necessary to scale to imaging larger volumes of tissue and tumor. We propose to: 1) Implement multiple techniques for CW acquisition to increase projection acquisition rate, select regions of interest and construct novel resonators 2) For pulsed image acquisition increase bandwidth and bandwidth uniformity as well as novel resonators and techniques to select regions of interest 3) Develop novel, even narrower line spin probes to with higher oxygen sensitivity 4) Build on the image acquisition and analysis progress. We hope to acquire a human image in the 5th year of support.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-SBIB-K (40))
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Sastre, Antonio
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University of Chicago
Schools of Medicine
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Redler, Gage; Epel, Boris; Halpern, Howard J (2014) EPR image based oxygen movies for transient hypoxia. Adv Exp Med Biol 812:127-33
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Tormyshev, Victor M; Rogozhnikova, Olga Yu; Bowman, Michael K et al. (2014) Preparation of Diversely Substituted Triarylmethyl Radicals by the Quenching of Tris(2,3,5,6-tetrathiaaryl)methyl Cations with C-, N-, P-, and S-Nucleophiles. European J Org Chem 2014:371-380
Redler, Gage; Epel, Boris; Halpern, Howard J (2014) Principal component analysis enhances SNR for dynamic electron paramagnetic resonance oxygen imaging of cycling hypoxia in vivo. Magn Reson Med 71:440-50
Epel, Boris; Redler, Gage; Halpern, Howard J (2014) How in vivo EPR measures and images oxygen. Adv Exp Med Biol 812:113-9
Epel, Boris; Bowman, Michael K; Mailer, Colin et al. (2014) Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance. Magn Reson Med 72:362-8
Elajaili, Hanan B; Biller, Joshua R; Eaton, Sandra S et al. (2014) Frequency dependence of electron spin-lattice relaxation for semiquinones in alcohol solutions. J Magn Reson 247:81-7
Redler, Gage; Epel, Boris; Halpern, Howard J (2014) What we learn from in vivo EPR oxygen images. Adv Exp Med Biol 812:121-6
Redler, Gage; Barth, Eugene D; Bauer Jr, Kenneth S et al. (2014) In vivo electron paramagnetic resonance imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl. Magn Reson Med 71:1650-6
Sundramoorthy, Subramanian V; Epel, Boris; Halpern, Howard J (2014) Orthogonal resonators for pulse in vivo electron paramagnetic imaging at 250 MHz. J Magn Reson 240:45-51

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