TOPAS - nBio, a Monte Carlo tool for radiation biology research

TOPAS - nBio，用于辐射生物学研究的蒙特卡罗工具

• 批准号: 9234495
• 负责人: Jan Patrick Oscar Schuemann
• 金额: $ 55.93万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234495
• 关键词: Address; Biological; Biological Models; Biology; Biophysics; Bystander Effect; Cell membrane; Cells; Cellular Structures; Chemical Models; Chemicals; Chemistry; Clinical; Clinical Trials; Code; Collaborations; Communication; Computer Simulation; Custom; DNA; Deposition; Development; Discipline; Dose; Foundations; Future; Geometry; Goals; Gold; Human body; Interdisciplinary Study; Lead; Learning; Libraries; Membrane; Microscopic; Mitochondria; Modeling; Monte Carlo Method; Nuclear; Organ; Patients; Physics; Process; RNA; Radiation; Radiation Physics; Radiation therapy; Radiobiology; Relative Biological Effectiveness; Research; Research Personnel; Signal Transduction; Structure; Testing; Tissues; Work; biological effect of radiation; cancer radiation therapy; detector; expectation; experimental study; flexibility; graphical user interface; improved; interdisciplinary collaboration; interest; nanoparticle; nanoscale; novel; novel strategies; particle; physical model; physical property; public health relevance; radiation effect; radiation response; response; simulation; subcellular targeting; tool; treatment planning

 DESCRIPTION (provided by applicant): Our goal is to develop a platform to contribute to deeper understanding of the interplay between radiation physics, chemistry and biology at sub-cellular levels and to facilitate interdisciplinary work on radiobiological research questions. Monte Carlo (MC) methods have been successfully employed to simulate physical properties of radiation, from the macroscopic dose deposition in radiation therapy patients down to the cellular scale to understand relative biological effectiveness. However, no tool currently provides accurate modeling of macroscopic as well as microscopic biological effects of radiation where researchers can define which interactions or structures (organ, cells and sub-cellular structures such as DNA, RNA or cell-membrane) are of interest. Furthermore, MC codes are nearly exclusively used by research physicists because their use requires a learning period that is generally too long for clinical physicists and biological researchers. We thus propose to build on a previously developed MC platform (TOPAS, a TOol for PArticle Simulation) and advance the physical and biological understanding across multiple levels through the detailed modeling of physical and chemical processes. We will offer a new approach to biological modeling by expanding TOPAS to the nanometer scale and include inter- and intra-cellular signaling and radiation response of sub-cellular components. This proposal will lay the foundation for a deeper understanding of the biological effects of radiation in tissues in order to facilitate new research at the boundary between physics and biology. To accomplish this we will: SA1: Customize MC for simulations of fluorescent nuclear track detectors (FNTD) and experimentally validate simulated particle track structures using these FNTDs. SA2: Facilitate chemical tracking of radicals and sub-cellular target (such as DNA, RNA, membrane, mitochondria) response simulation within MC. SA3: Develop a graphical user interface (GUI) and provide an extensible library of sub-cellular geometry components that can be easily exchanged among researchers. SA4: Develop specific model scenarios to carry out foundational research in four selected research topics. The resulting tool, TOPAS-nBio, will facilitate the exchange of ideas and results between physicists and biologists. The flexibility of the proposed TOPAS-nBio, together with open exchange of cell components among researchers, will facilitate communication across fields provide the basis for interdisciplinary collaborations and provide a tool to advance understanding of biological responses to radiation.

 描述（由申请人提供）：我们的目标是开发一个平台，有助于更深入地了解亚细胞水平上的辐射物理、化学和生物学之间的相互作用，并促进放射生物学研究问题的跨学科工作。蒙特卡罗 (MC) 方法已成功用于模拟辐射的物理特性，从放射治疗患者的宏观剂量沉积到细胞尺度，以了解相对的生物有效性。不过目前还没有工具提供 对辐射的宏观和微观生物效应进行精确建模，研究人员可以定义感兴趣的相互作用或结构（器官、细胞和亚细胞结构，如 DNA、RNA 或细胞膜）。此外，MC 代码几乎专门由研究物理学家使用，因为它们的使用需要一个学习期，而这对于临床物理学家和生物研究人员来说通常太长。因此，我们建议建立在先前开发的 MC 平台（TOPAS，粒子模拟工具）的基础上，通过物理和化学过程的详细建模，在多个层面上推进物理和生物理解。我们将通过将 TOPAS 扩展到纳米尺度，提供一种新的生物建模方法，包括细胞间和细胞内信号传导以及亚细胞成分的辐射响应。该提案将为更深入地了解辐射对组织的生物效应奠定基础，以促进新的研究 处于物理学和生物学之间的边界。为了实现这一目标，我们将： SA1：定制 MC 以模拟荧光核径迹探测器 (FNTD)，并使用这些 FNTD 通过实验验证模拟粒子径迹结构。 SA2：促进 MC 内自由基和亚细胞靶标（如 DNA、RNA、膜、线粒体）反应模拟的化学追踪。 SA3：开发图形用户界面（GUI）并提供可在研究人员之间轻松交换的可扩展的亚细胞几何组件库。 SA4：开发具体的模型场景，在四个选定的研究主题中开展基础研究。由此产生的工具 TOPAS-nBio 将促进物理学家和生物学家之间的思想和结果的交流。所提出的 TOPAS-nBio 的灵活性，加上研究人员之间细胞成分的开放交换，将促进跨领域的交流，为跨学科合作奠定基础，并提供一种工具来促进对辐射的生物反应的理解。