School of Nuclear Science and Engineering, Oregon State University, 100 Radiation Center, Corvallis, OR 97331, United States of America.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63110, United States of America.
Phys Med Biol. 2021 Feb 11;66(4):045026. doi: 10.1088/1361-6560/abd4f9.
Understanding and designing clinical radiation therapy is one of the most important areas of state-of-the-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that facilitates building of the sophisticated multi-cell-based model of how radiation affects the biology of living tissue. We designed and implemented a coupled simulation method, including a radiation transport model, and a cell biology model, to simulate the tumor response after irradiation. The radiation transport simulation was implemented through Geant4 which is an open-source Monte Carlo simulation platform that provides many flexibilities for users, as well as low energy DNA damage simulation physics, Geant4-DNA. The cell biology simulation was implemented using CompuCell3D (CC3D) which is a cell biology simulation platform. In order to couple Geant4 solver with CC3D, we developed a 'bridging' module, RADCELL, that extracts tumor cellular geometry of the CC3D simulation (including specification of the individual cells) and ported it to the Geant4 for radiation transport simulation. The cell dose and cell DNA damage distribution in multicellular system were obtained using Geant4. The tumor response was simulated using cell-based tissue models based on CC3D, and the cell dose and cell DNA damage information were fed back through RADCELL to CC3D for updating the cell properties. By merging two powerful and widely used modeling platforms, CC3D and Geant4, we delivered a novel tool that can give us the ability to simulate the dynamics of biological tissue in the presence of ionizing radiation, which provides a framework for quantifying the biological consequences of radiation therapy. In this introductory methods paper, we described our modeling platform in detail and showed how it can be applied to study the application of radiotherapy to a vascularized tumor.
理解和设计临床放射治疗是最先进的肿瘤治疗方案中最重要的领域之一。几十年来，人们一直在研究开发复杂的治疗设备和优化方案，以确定时间表和剂量。在本文中，我们提出了一个全面的计算平台，该平台有助于构建复杂的多细胞模型，以研究辐射如何影响活组织的生物学。我们设计并实现了一种耦合模拟方法，包括辐射传输模型和细胞生物学模型，以模拟照射后肿瘤的反应。辐射传输模拟是通过 Geant4 实现的，Geant4 是一个开源的蒙特卡罗模拟平台，为用户提供了许多灵活性，以及用于低能 DNA 损伤模拟的物理引擎 Geant4-DNA。细胞生物学模拟是使用 CompuCell3D（CC3D）实现的，CC3D 是一个细胞生物学模拟平台。为了将 Geant4 求解器与 CC3D 耦合，我们开发了一个名为 RADCELL 的“桥接”模块，该模块提取 CC3D 模拟中的肿瘤细胞几何形状（包括单个细胞的指定），并将其移植到 Geant4 中进行辐射传输模拟。使用 Geant4 获得多细胞系统中的细胞剂量和细胞 DNA 损伤分布。使用基于 CC3D 的细胞组织模型模拟肿瘤反应，并通过 RADCELL 将细胞剂量和细胞 DNA 损伤信息反馈给 CC3D，以更新细胞属性。通过合并两个强大且广泛使用的建模平台 CC3D 和 Geant4，我们提供了一种新工具，可以模拟存在电离辐射时生物组织的动力学，为量化放射治疗的生物学后果提供了框架。在这篇介绍性方法论文中，我们详细描述了我们的建模平台，并展示了如何将其应用于研究放射治疗在血管化肿瘤中的应用。
