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: 10655343
• 负责人: WESLEY E BOLCH
• 金额: $ 47.24万
• 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/10655343
• 关键词: 3-Dimensional; Adolescent; Adult; Angiography; Blood; Blood Circulation; Blood Vessels; Blood Volume; Blood flow; 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; Marrow; Measures; Methodology; Methods; Modality; Modeling; Mus; Nature; Organ; Patient Representative; Patients; Population; Radiation; Radiation Dose Unit; Radiation Interaction; Radiation Oncology; Radiation therapy; Research; Risk; Rodent; Site; Structure; Time; Treatment Protocols; biomathematics; cell killing; cortical bone; design; dosimetry; ex vivo imaging; in vivo imaging; innovation; irradiation; lymph nodes; lymphoid organ; male; 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/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 我们预计放射肿瘤学的未来治疗计划将包括血液（即循环淋巴细胞）。 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。 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 然而，该工具是使用生物数学的先决条件。 本研究中开发的模型将是第一个解决这一紧迫问题的模型。 除了其整体创新性之外，还需要放射治疗和研究界。 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)

项目成果

Predicting Severity of Radiation Induced Lymphopenia in Individual Proton Therapy Patients for Varying Dose Rate and Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations.

使用动态 4 维血流模拟预测不同剂量率和分割的质子治疗个体患者中放射引起的淋巴细胞减少症的严重程度。

• 发表时间: 2023-08-01
• 作者: McCullum, Lucas;Shin, Jungwook;Xing, Stella;Beekman, Chris;Schuemann, Jan;Hong, Theodore;Duda, Dan;Mohan, Radhe;Lin, Steven H;Correa;Domal, Sean;Withrow, Julia;Bolch, Wesley;Paganetti, Harald;Grassberger, Clemens
• 通讯作者: Grassberger, Clemens

A dynamic blood flow model to compute absorbed dose to circulating blood and lymphocytes in liver external beam radiotherapy.

动态血流模型，用于计算肝脏外照射放射治疗中循环血液和淋巴细胞的吸收剂量。

• 发表时间: 2022-02-15
• 影响因子: 3.5
• 作者: Xing, Shu;Shin, Jungwook;Pursley, Jennifer;Correa;Depauw, Nicolas;Domal, Sean;Withrow, Julia;Bolch, Wesley;Grassberger, Clemens;Paganetti, Harald
• 通讯作者: Paganetti, Harald

MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

MIDOS：一种针对肝肿瘤微球剂量测定治疗计划系统的新型随机模型。

• 发表时间: 2024-05
• 影响因子: 9.1
• 作者: Huesa;Withrow, Julia D;Dawson, Robert J;Beekman, Chris;Bolch, Wesley E;Paganetti, Harald;Wehrenberg;Bertolet, Alejandro
• 通讯作者: Bertolet, Alejandro

4D blood flow model for dose calculation to circulating blood and lymphocytes.

用于计算循环血液和淋巴细胞剂量的 4D 血流模型。

• 发表时间: 2020-03-02
• 影响因子: 3.5
• 作者: Hammi, Abdelkhalek;Paganetti, Harald;Grassberger, Clemens
• 通讯作者: Grassberger, Clemens

HEDOS-a computational tool to assess radiation dose to circulating blood cells during external beam radiotherapy based on whole-body blood flow simulations.

HEDOS - 一种计算工具，用于基于全身血流模拟评估外照射放射治疗期间循环血细胞的辐射剂量。

• 发表时间: 2021-08-03
• 影响因子: 3.5
• 作者: Shin, Jungwook;Xing, Shu;McCullum, Lucas;Hammi, Abdelkhalek;Pursley, Jennifer;Correa, Camilo A;Withrow, Julia;Domal, Sean;Bolch, Wesley;Paganetti, Harald;Grassberger, Clemens
• 通讯作者: Grassberger, Clemens