In this preclincal study, Dr. Sara Rapic (former Post-doctoral fellow) and Timothy Samuel (Ph.D. candidate) demonstrated the improved accuracy of using 3-dimensional bioluminescence imaging (BLI) to deliver targeted high dose radiotherapy in orthotopic mouse models of pancreatic cancer. This BLI image-guided precision in the delivery of radiation therapy to pancreatic tumors in vivo ensures the precision of the treatment using a novel small animal irradiator. This methodology allows us to investigate the response of these tumors, their vasculature and microenvironment to radiation therapy tailored to simulate clinical radiotherapy regimes in patients. This technology is also helping to expand our understanding of tumor hypoxia in pancreatic cancer and how hypoxia can impact tumor response as well as modify the tumor microenvironment over time. Currently, this platform is being used to study the relationship between pancreatic tumor cell hypoxia and changes in tumor-associated stromal cells in vivo in the orthotopic setting by exploiting our intravital fluorescence imaging platform with and without radiation treatment.