a) Scaling up of resonant structures to enable imaging larger objects for pO2. We have achieved, in prior years the capability of studying tumor bearing mice for oxygen status. Image formation and reconstruction techniques were developed and implemented to obtain images with useful spatial and temporal resolutions. Such efforts will provide experience to translate this imaging modality to study humans, at least local regions to obtain important physiological information. We have designed, constructed, tested and successfully implemented a four-channel coil array which quadrupled the volume which can accommodate larger objects the size of rat/rabbit. This size makes studies of tumors such as head and neck, breast, and prostate. b) Accelerated imaging of tumor oxygenation using EPRI to allow monitoring dynamics of tumor oxygen. Most imaging techniques using tracers for hypoxia and PET imaging obtain a static picture of the tumor oxygen status. But many pre-clinical studies in experimental animals suggest that oxygen supply in tumors is a dynamic phenomenon with regions of chronic hypoxia and regions with cycling hypoxia. EPRI, intrinsically being a technique which uses a paramagnetic tracer on which oxygen molecule imposes a contrast, allows obtaining maps of oxygen without actually consuming it as in the case of an electrode or reports indirectly as in PET. To allow examining the dynamics of tumor oxygenation, the temporal resolution of EPRI has been significantly improved using a model based reconstruction approach allowing us to take a 3-D snap shot in under 1 min. c) With the improvements in imaging of tumor oxygen dynamics, it was possible to use EPR imaging to synergize the efficacy of the hypoxia activated prodrug TH-302 with prior administration of pyruvate to increase hypoxia. Pyruvate, which is used to image metabolism has also been found to increase transiently tumor hypoxia, as detected by EPRI. Since TH-302 is a hypoxia selective toxin, increasing hypoxia with pyruvate may increase its efficacy. EPRI was used to determine the treatment schedule.
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