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: 10214573
• 负责人: WESLEY E BOLCH
• 金额: $ 49.05万
• 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/10214573
• 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 这项建议将开发量化辐射与免疫系统相互作用的方法，特别是 血液(即循环中的淋巴细胞)。我们预计，未来放射肿瘤学的治疗计划将 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程度。在.期间 放射治疗，循环中淋巴细胞的耗竭主要源于(1)在放射治疗过程中立即杀死细胞 照射治疗视野内的血管，从而照射循环中的淋巴细胞，以及(2)照射到较小的 对驻留在淋巴器官内可动员其淋巴细胞的淋巴细胞的辐射剂量 人口对系统性枯竭的影响。 目前还没有可用于计算血液的全身计算模体 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 临床试验设计的模型。这项研究中将要开发的幻影将首先填补这一紧迫的 需要放射治疗和研究界。除了总体上的创新性质外，这 项目中，我们有几种方法是新颖的，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) ·首次实施全身隔室血液流动模型(SA2) ·首次使用血管结构对血液流动进行四维建模(SA3) ·用于临床前研究的第一个小鼠血管系统模型(SA4)