Project Abstract / Summary This proposal will develop methods to quantify the interaction of radiation with the immune system, particularly the blood (i.e., circulating lymphocytes). We envision that future treatment planning in radiation oncology will treat lymphatic nodes and the blood as organs at risk and include them in the treatment optimization process so as to influence the level at which the radiation treatment impacts the immune system of the patient. During radiation therapy, depletion of circulating lymphocytes originates mainly from (1) immediate cell killing during irradiation of blood vessels, and thus circulating lymphocytes, within the treatment field and (2) to a lesser extent, the radiation dose to lymphocytes residing within lymphoid organs that can mobilize their lymphocyte population upon systemic depletion. There are currently no whole-body computational phantoms available that can facilitate the calculation of blood or lymphocyte dose-volume histograms. However, this tool is a prerequisite to the use of bio-mathematical models for clinical trial design. The phantoms to be developed in this study will be the first to fill this urgent need for the radiation therapy and research communities. In addition to the overall innovative nature of this project, several of our methods are novel and have never been employed in our field: • The first use of tetrahedral mesh structures to model blood vessels (SA1) • The first implementation of a whole-body compartment model for blood flow (SA2) • The first four-dimensional modeling of blood flow using vasculature structures (SA3) • The first model of the mouse vasculature for pre-clinical studies (SA4)