Development of a coupled simulation toolkit for computational radiation biology based on Geant4 and CompuCell3D

Abstract

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.

Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations

“…Hereby the prediction of cell-survival is the benchmark for testing new models [232]. Going beyond isolated cells to study phenomena such as the radiation induced bystander effect [222] or the radiation response on a tissue level [223] are still in an early stage. However, complete multiscale models including AuNP radiosensitization of DNA into a xenograft mouse model highlight already what can be achieved by integration and combination of simulation and modelling techniques on different scales [258].…”

“…Their term refers to cells which die or show choromosomal instability without having been directly irradiated during a treatment, as observed by Nagasawa and Little [219] after subjecting Chinese hamster ovary cells (CHO) to low doses of alpha particles, or by Sedelnikova et al which found DSB in bystander cells after irradiation of a human tissue models by a microbeam [220]. To study these effects with a multi-scale approach Geant4 and CompuCell3D [221] were combined by Liu et al via a newly developed bridging module named RADCELL [222]. This allowed them to combined simulations of cell biology and particlescattering simulations to study and quantifying cell behavior after irradiation.…”

Nuclear Data for High Energy Ion Interactions and Secondary Particle Production

“…One is the GEANT4-DNA code, a low-energy extension of GEANT4 that enables studies of the cellular radiobiological effects of ionizing radiation on DNA, considering the physical, chemical, and biological stages of the interactions. GEANT4 has also been coupled to the CompuCell3D cell biology simulation platform via the RADCELL module [85], enabling tumor geometries to be ported to the transport code. The ion stopping powers in various materials are key inputs for these codes.…”

Shaping the Organ: A Biologist Guide to Quantitative Models of Plant Morphogenesis

“…Outside of plant world other frameworks could be adapted to model plant organs such as CompuCell3D ( Cickovski et al, 2005 ) – a lattice-based multicellular modeling environment to simulate tissue formation by merging the CPM with chemical fields and diffusion equations. CompuCell3D functionalities have been demonstrated in the context of animal embryogenesis, cell population dynamics, tumor formation, and many more ( Andasari et al, 2012 ; Swat et al, 2012 ; Fortuna et al, 2020 ; Liu et al, 2021 ). Another valuable tool to simulate animal embryogenesis is MecaGen, a C++ simulation platform of animal multicellular development relying on mechanistic agent-based models ( Delile et al, 2017 ).…”