Development of Models of Comprehensive Blood and Lymphatic Systems for Radiation Dosimetry

PROJECT SUMMARY Radiation induced lymphopenia (RIL) occurs in approximately one-half of cancer patients receiving external beam radiotherapy and this post-therapy condition has been shown to greatly reduce five-year survival rates. It is theorized that RIL is induced by direct lymphocyte cell kill, suggesting that assessment of the radiation dose to lymphocytes during radiotherapy is a necessary requirement for their consideration as a dose avoidance structure. In order to facilitate the computation of radiation dose to circulating lymphocytes, their supporting structures must be modeled in patient anatomic models used in tissue dosimetry. Currently, there exists no intra- organ blood vasculature nor lymphatic vasculature nor specialized lymphoid tissue structures within the International Commission on Radiological Protection’s (ICRP) reference computational phantoms – commonly used as a digital model of medical patients. Additionally, there exists major inaccuracies in the inter-organ whole- body blood vessels of these reference phantoms, and no modeling of microscale vasculature of blood or lymph has been yet undertaken to account for their large portion blood and lymph within the human body. Additionally, in applications of radiopharmaceutical therapy, blood self-dose, which is substantial for short-range radiations such as alpha particles and lower-energy electrons, emitted by many common radiopharmaceuticals, cannot be entirely quantified due to the lack of intra-organ vasculature in the ICRP phantoms. Dose to lymphatic vessels, additionally can be computed for the first time in RPT applications with these models in place. Therefore, this project hypothesizes that the development of a comprehensive model of blood and lymphatic vessels and corresponding lymphoid tissues will facilitate the computation of blood and lymphocyte radiation dose for the first time and will subsequently allow for consideration of circulating and non-circulating lymphocytes as organs-at- risk in radiotherapy treatment planning. The proposed project will be achieved by the completion of four Specific Aims: Aim 1: develop whole-body adult mesh models with intra-organ and inter-organ vasculature. Aim 2: develop corresponding lymphatic tissue and vessel models. Aim 3: develop organ specific microscale blood and lymph vasculature models. Aim 4: compute organ radionuclide S values for radiopharmaceutical therapy and lymphocyte dosimetry for external beam radiotherapy. Completion of these aims will greatly improve the computational models used as tools in reference medical dosimetry for a new assessment of dose to blood, as well as set the stage for adaptation of these models via deformable registration to expand to patient-specific modeling and personalized dosimetry.