Megavoltage radiation beams used in External Beam Radiotherapy (EBRT) generate Cherenkov light emission in tissues and equivalent phantoms. This optical emission was utilized to excite an oxygen-sensitive phosphorescent probe, PtG4, which has been developed specifically for NIR lifetime-based sensing of the partial pressure of oxygen (pO 2 ). Phosphorescence emission, at different time points with respect to the excitation pulse, was acquired by an intensifier-gated CCD camera synchronized with

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... radiation pulses delivered by a medical linear accelerator. The pO 2 distribution was tomographically recovered in a tissue-equivalent phantom during EBRT with multiple beams targeted from different angles at a tumor-like anomaly. The reconstructions were tested in two different phantoms that have fully oxygenated background, to compare a fully oxygenated and a fully deoxygenated inclusion. To simulate a realistic situation of EBRT, where the size and location of the tumor is well known, spatial information of a prescribed region was utilized in the recovery estimation. The phantom results show that region-averaged pO2 values were recovered successfully, differentiating aerated and deoxygenated inclusions. Finally, a simulation study was performed showing that pO 2 in human brain tumors can be measured to within 15mmHg for edge depths less than 10-20mm using the Cherenkov Excited Phosphorescence Oxygen imaging (CEPhOx) method and PtG4 as a probe. This technique could allow non-invasive monitoring of pO 2 in tumors during the normal process of EBRT, where beams are generally delivered from multiple angles or arcs during each treatment fraction.