Developing whole-body computational phantoms for blood dosimetry to model the impact of radiation on the immune system

项目摘要/总结 该提案将开发量化辐射与免疫系统相互作用的方法，特别是 血液（即循环淋巴细胞）。我们预计放射肿瘤学的未来治疗计划将 将淋巴结和血液视为有风险的器官，并将其纳入治疗优化过程 从而影响放射治疗对患者免疫系统的影响水平。期间 放射治疗时，循环淋巴细胞的耗竭主要源于（1）放射治疗过程中的立即细胞杀伤 照射治疗区域内的血管，从而照射循环淋巴细胞，并且 (2) 减少 范围内，对驻留在淋巴器官内的淋巴细胞的辐射剂量，可以动员其淋巴细胞 系统性枯竭后的人口。 目前还没有可以方便计算血液的全身计算模型 或淋巴细胞剂量体积直方图。然而，这个工具是使用生物数学的先决条件。 临床试验设计模型。本研究中开发的模型将是第一个填补这一紧迫问题的模型。 放射治疗和研究界的需求。除了整体的创新性之外 项目中，我们的一些方法是新颖的，从未在我们的领域中使用过： • 首次使用四面体网格结构来模拟血管（SA1） • 首次实施血流全身室模型 (SA2) • 第一个使用脉管系统结构的血流四维建模 (SA3) • 第一个用于临床前研究的小鼠脉管系统模型 (SA4)

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)