TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology

Abstract

The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

“…Applying the stochastic quantity lineal energy in microdosimetry and considering the spectral distribution of lineal energy may better correlate biological outcome with physical interactions between ionizing radiations and biological systems 28 . The microdosimetric spectra can be measured using a tissue-equivalent proportional counter (TEPC) [44][45][46] and from Monte Carlo simulations [47][48][49][50] . Comparing the predictions using microdosimetry-based RBE models such as MKM [51][52][53] and RMF [54][55][56] with experimental data is an ideal future application of our high-throughput system.…”

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

“…The simulations presented here were performed using the TOPAS-nBio, an extension of TOPAS version 3.1.p3 which is based on Geant4 version 10.3.p1. TOPAS-nBio [81] is an extension aiming to provide the ease of use provided by TOPAS to simulations at the nanometer scale for cellular and sub-cellular radiobiology using Geant4-DNA physics and chemistry models. The default Geant4-DNA (option 0) was used for the simulation of particle transport within water but Geant4-DNA currently does not include cross sections for gold.…”

Ionizing Radiation and Complex DNA Damage: Quantifying the Radiobiological Damage Using Monte Carlo Simulations

“…Geant4-DNA can transport electrons (7.4 eV-1 MeV), protons (100 eV-100 MeV), alpha particles (1 keV-400 MeV), and ions (0.5 MeV/u-10 6 MeV/u). It is noteworthy that the TOPAS-nBio software [90], which extends the TOPAS MC code [91] to the (sub) cellular and DNA scale for radiobiological studies [92], is based on the Geant4-DNA package.…”