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.