ABSTRACT Optical imaging of Cherenkov emission from tissue during radiotherapy has been demonstrated in humans, providing a map correlated to radiation dose within the surface tissues. In external beam radiotherapy, the signal is optimally captured by time-gated intensified cameras, synchronized to the linear accelerator pulses, allowing rejection of the majority of background room light, and providing real time video of each radiotherapy treatment with standard dose rates. This discovery combined with CT and reflectance calibration has the potential to allow accurate quantitative dose imaging in humans for the first time in the history of therapeutic radiation use. While the imaging technology has inherent limitations to surface regions, the fact that it is a real time imaging tool and provide visual recording of every feature of a treatment plan is revolutionary. It has the potential for a paradigm change in how radiotherapy is documented and archived for daily reliance, quality audit and potentially automated control of delivery. The implementation of Cherenkov imaging is significantly simpler than most dosimetry tools, however the understanding and interpretation of the images need to be established, in order to be clear about what is possible in imaging delivery of dose. This proposed technology developments advance the methods for quantitative dose imaging in whole breast radiation treatment using our patented approach to CT/reflectance calibration of Cherenkov imaging, will be advanced and tested in regular treatments. Additionally, we will advance the ability to image patients with complex multi-field treatments, where adjacent beam fields are matched, so that we can quantify the dose accuracy at the match lines. Another application is treatment of total skin with electron therapy, where the field is extremely large and so imaging dosimetry makes sense. Our preliminary data indicates that areas of chronic underexposure exist today and the optimal delivery technique will be defined by our efforts in imaging and 3D animation & visualization of total body skin dose, developing an optimized imaging system to identify the ideal treatment technique for patients of different body shape. Finally, Cherenkov imaging is synergistic with scintillator imaging of dose, and this will be advanced as a related tool to remotely quantify skin dose. Taken together, this project will advance the only way to directly image radiotherapy dose and delivery on the patient’s tissue. The core of the project is combined technology systems, leveraging a large installed base of cameras and national partnerships advancing this field. This technology is embryonic but on the cusp of commercialization, where the focus of this research project being to advance the science and methods of where it can add value to radiotherapy. The long term benefit of advancing this technology will be to change the way in which radiotherapy incidents are observed by the therapist team and ha...