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

Area of Science:

• Medical Physics
• Radiation Biology
• Computational Biology

Background:

• TOPAS Monte Carlo (MC) is crucial for proton therapy research, simulating patient-scale properties.
• Understanding cellular and sub-cellular responses to radiation is vital for radiobiology.
• Existing MC tools lack detailed modeling of biological effects at the cellular level.

Purpose of the Study:

• Develop TOPAS-nBio, an extension of TOPAS for radiobiological research at the cellular and sub-cellular scales.
• Integrate detailed physics and chemistry simulations for radiobiological experiments.
• Advance the understanding of radiation-induced DNA damage and repair mechanisms.

Main Methods:

• Extended TOPAS using Geant4-DNA for low-energy particle interactions and track-structure simulations.
• Incorporated chemical reactions within the first millisecond and specialized cell geometries.
• Developed a new Independent Reaction Times (IRT) method for faster chemical stage simulations.
• Modeled DNA double-strand break (DSB) induction in DNA fibers for proton irradiations.

Main Results:

• TOPAS-nBio simulations showed good agreement with experimental data for energy deposition and chemical reaction rates.
• The IRT method accelerated chemical stage simulations by a factor of 145.
• Over 50% of induced DSBs involved chemical reactions, with 5% solely caused by them.
• Simulations provided initial yields of DSBs for 3 and 50 MeV proton irradiations.

Conclusions:

• TOPAS-nBio provides accurate, multiscale simulations from radiation fields to cellular outcomes.
• The extension facilitates detailed physics and chemistry simulations of radiobiological experiments.
• TOPAS-nBio aids in understanding initial radiation-induced damage and links to DNA repair models.