Author: Alejandro Bertolet, Jorge Naoki Dominguez Kondo, Bruce A. Faddegon, Kathryn D Held, Nicolas Henthorn, Jay LaVerne, Thongchai Masilela, Stephen J. McMahon, Isaac Meyer, Victor V. Onecha, Harald Paganetti, Jose A. Ramos-Mendez, Jan PO Schuemann, Wook-Geun Shin, Michael Taylor, John Warmenhoven 👨🔬
Affiliation: Massachusetts General Hospital, Queen's University Belfast, Massachusetts General Hospital and Harvard Medical School, University of California San Francisco, University of Manchester, Notre Dame University 🌍
Purpose: TOPAS-nBio brings a cutting-edge Monte Carlo (MC) simulation framework to the research community to test hypotheses of radiation effects at the nanometer/cell scale. Here, we present the developments and progress made over the last decade of the TOPAS-nBio project.
Methods: TOPAS-nBio extends the TOPAS MC application, which has recently been released as OpenTOPAS v4.0 (https://opentopas.github.io), to a platform for nanoscopic modeling of the biological effects of ionizing radiation. TOPAS-nBio/TOPAS is built on the Geant4 MC toolkit and its extension to the nanoscopic scale, Geant4-DNA. The TOPAS-nBio project links detailed MC track-structure simulations with precise geometrical representations of (sub-)cellular components, including initial chemical processes and likely biological outcomes via mechanistic models of DNA repair.
Results: The latest TOPAS-nBio release v3.0 (https://github.com/topas-nbio) provides a simulation framework for nanometer scale radiobiology research. We have developed a variety of geometries, including multiple cell topologies and different representations of DNA geometries, including cell-line specific DNA representations using Hi-C data. Energy depositions can be scored to obtain induction of direct DNA damage after irradiation or indirect DNA damage following chemical reactions after radiolysis. Special emphasis was given to expanding the chemistry framework, improving simulation speed using the independent reaction time method, expanding the simulated time to include long-term reactions by merging non-homogeneous and homogeneous chemistry stages, adding chemistry mimicking cell environments, including reactions with DNA constituents, and the capability to simulate ultra-high dose-rate irradiation. Two models of DNA repair kinetics have been linked to predict final biological effects.
Conclusion: TOPAS-nBio offers cross-disciplinary simulations aiming to understand cell-level radiobiology, and has been applied internationally by multiple groups, providing insights into mechanisms of cell responses for different radiation modalities or when investigating new technologies (e.g., nanoparticles or FLASH).