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

开发用于血液剂量测定的全身计算模型，以模拟辐射对免疫系统的影响

• 批准号: 10429988
• 负责人: WESLEY E BOLCH
• 金额: $ 47.78万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-13 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429988
• 关键词: 3-Dimensional; Adolescent; Adult; Angiography; Blood; Blood Circulation; Blood Vessels; Blood Volume; Blood flow; Bone Marrow; Clinical Research; Clinical Trials; Clinical Trials Design; Combination immunotherapy; Communities; Corrosion Casting; Dose; Female; Four-dimensional; Fractionation; Future; Goals; Immune response; Immune system; Laboratory mice; Libraries; Lymphocyte; Male Adolescents; Measures; Methodology; Methods; Modality; Modeling; Mus; Nature; Organ; Patient Representative; Patients; Population; Radiation; Radiation Dose Unit; Radiation Interaction; Radiation Oncology; Radiation therapy; Risk; Rodent; Site; Structure; Therapeutic Studies; Time; Treatment Protocols; base; cell killing; cortical bone; design; dosimetry; ex vivo imaging; in vivo imaging; innovation; irradiation; lymph nodes; lymphoid organ; male; mathematical model; microCT; mouse model; novel; pre-clinical research; preclinical study; process optimization; simulation; skeletal; tool; treatment optimization; treatment planning

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)

项目摘要 /摘要 该建议将开发方法来量化辐射与免疫系统的相互作用，特别是 血液（即循环淋巴细胞）。我们设想，放射肿瘤学中未来的治疗计划将 将淋巴结淋巴结和血液作为有风险的器官，并将其包括在治疗优化过程中 以影响辐射治疗影响患者免疫系统的水平。期间 放射疗法，循环淋巴细胞的耗竭主要起源于（1）立即杀死在 血管的照射，从而在治疗领域内循环淋巴细胞，（2）较小 范围，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 全身部署的人口。 当前没有可用的全身计算幻象可以促进血液的计算 或淋巴细胞剂量 - 体积直方图。但是，此工具是使用生物数学的先决条件 临床试验设计模型。本研究中要开发的幻影将是第一个填补这一紧急的幻象 需要放射疗法和研究社区。除了总体创新性质 项目，我们的几种方法是新颖的，从未在我们的领域雇用： •首次使用四面体网状结构对血管建模（SA1） •首先实施了血流的全身隔室模型（SA2） •使用脉管系统结构（SA3）对血流的第一个四维建模（SA3） •用于临床前研究的小鼠脉管系统的第一个模型（SA4）