Purpose . We present a microscopic mechanism that accounts for the outward burst of ‘cold’ ion species (IS) in a high-energy particle track due to coupling with ‘hot’ non-ion species (NIS). IS refers to radiolysis products of ionized molecules, whereas NIS refers to non-ionized excitations of molecules in a medium. The interaction is mediated by a quantized field of acoustic phonons, a channel that allows conversion of thermal energy of NIS to kinetic energy of IS, a flow of heat from the outer to the inner core of the track structure. Methods . We perform step-by-step Monte Carlo (MC) simulations of ionizing radiation track structures in water to score the spatial coordinates and energy depositions that form IS and NIS at atto-second time scales. We subsequently calculate the resulting temperature profiles of the tracks with MC track structure simulations and verify the results analytically using the Rutherford scattering formulation. These temperature profiles are then used as boundary conditions in a series of multi-scale atomistic molecular dynamic (MD) simulations that describe the sudden expansion and enhanced diffusive broadening of tracks initiated by the non-equilibrium spectrum of high-energy IS. We derive a stochastic coarse-grained Langevin equation of motion for IS from first-principle MD to describe the irreversible femto-second flow of thermal energy pumping from NIS to IS, mediated by quantized fields of acoustic phonons. A pair-wise Lennard-Jones potential implemented in a classical MD is then employed to validate the results calculated from the Langevin equation. Results . We demonstrate the coexistence of ‘hot’ NIS with ‘cold’ IS in the radiation track structures right after their generation. NIS, concentrated within nano-scale volumes wrapping around IS, are the main source of intensive heat-waves and the outward burst of IS due to femto-second time scale IS-NIS coupling. By comparing the transport of IS coupled to NIS with identical configurations of non-interacting IS in thermal equilibrium at room temperature, we demonstrate that the energy gain of IS due to the surrounding hot nanoscopic volumes of NIS significantly increases their effective diffusion constants. Comparing the average track separation and the time scale calculated for a deposited dose of 10 Gy and a dose rate of 40 Gy s ⁻¹ , typical values used in FLASH ultra high dose rate (UHDR) experiments, we find that the sudden expansion of tracks and ballistic transport proposed in this work strengthens the hypothesis of inter-track correlations recently introduced to interpret mitigation of the biological responses at the FLASH-UHDR (Abolfath et al 2020 Med. Phys. 47 , 6551–6561). Conclusions . The much higher diffusion constants predicted in the present model suggest higher inter-track chemical reaction rates at FLASH-UHDR, as well as lower intra-track reaction rates. This study explains why research groups relying on the current Monte Carlo frameworks have reported negligible inter-track overlaps, simply because of underestimation of the diffusion constants. We recommend incorporation of the IS-NIS coupling and heat exchange in all MC codes to enable these tool-kits to appropriately model reaction-diffusion rates at FLASH-UHDR. Novelty . To introduce a hypothetical pathway of outward burst of radiolysis products driven by highly localized thermal spikes wrapping around them and to investigate the interplay of the non-equilibrium spatio-temporal distribution of the chemical activities of diffusive high-energy particle tracks on inter-track correlations at FLASH-UHDR.

The radiation-induced damages in bio-molecules are ubiquitous processes in radiotherapy and radio-biology, and critical to space projects. In this study, we present a precise quantification of the fragmentation mechanisms of deoxyribonucleic acid (DNA) and the molecules surrounding DNA such as oxygen and water under non-equilibrium conditions using the first-principle calculations based on density functional theory (DFT). Our results reveal the structural stability of DNA bases and backbone that withstand up to a combined threshold of charge and hydrogen abstraction owing to simultaneously direct and indirect ionization processes. We show the hydrogen contents of the molecules significantly control the stability in the presence of radiation. This study provides comprehensive information on the impact of the direct and indirect induced bond dissociations and DNA damage and introduces a systematic methodology for fine-tuning the input parameters necessary for the large-scale Monte Carlo simulations of radio-biological responses and mitigation of detrimental effects of ionizing radiation.

We introduce an approach for global fitting of the recently published high-throughput and high accuracy clonogenic cell-survival data for therapeutic scanned proton beams. Our fitting procedure accounts for the correlation between the cell-survival, the absorbed (physical) dose and the proton linear energy transfer (LET). The fitting polynomials and constraints have been constructed upon generalization of the microdosimetric kinetic model (gMKM) adapted to account for the low energy and high lineal-energy spectrum of the beam where the current radiobiological models may underestimate the reported relative biological effectiveness (RBE). The parameters (α, β) of the linear-quadratic (LQ) model calculated by the presented method reveal a smooth transition from low to high LETs which is an advantage of the current method over methods previously employed to fit the same clonogenic data. Finally, the presented approach provides insight into underlying microscopic mechanisms which, with future study, may help to elucidate radiobiological responses along the Bragg curve and resolve discrepancies between experimental data and current RBE models.

Auger cascades generated in high atomic number nanoparticles (NPs) following ionization were considered a potential mechanism for NP radiosensitization. In this work, we investigated the microdosimetric consequences of the Auger cascades using the theory of dual radiation action (TDRA), and we propose the novel Bomb model as a general framework for describing NP-related radiosensitization. When triggered by an ionization event, the Bomb model considers the NPs that are close to a radiation sensitive cellular target, generates dense secondary electrons and kills the cells according to a probability distribution, acting like a “bomb.” TDRA plus a distance model were used as the theoretical basis for calculating the change in α of the linear-quadratic survival model and the relative biological effectiveness (RBE). We calculated these quantities for SQ20B and Hela human cancer cells under 250 kVp X-ray irradiation with the presence of gadolinium-based NPs (AGuIX^TM), and 220 kVp X-ray irradiation with the presence of 50 nm gold NPs (AuNPs), respectively, and compared with existing experimental data. Geant4-based Monte Carlo (MC) simulations were used to (1) generate the electron spectrum and the phase space data of photons entering the NPs and (2) calculate the proximity functions and other related parameters for the TDRA and the Bomb model. The Auger cascade electrons had a greater proximity function than photoelectric and Compton electrons in water by up to 30%, but the resulting increases in α were smaller than those derived from experimental data. The calculated RBEs cannot explain the experimental findings. The relative increase in α predicted by TDRA was lower than the experimental result by a factor of at least 45 for SQ20B cells with AGuIX under 250 kVp X-ray irradiation, and at least four for Hela cells with AuNPs under 220 kVp X-ray irradiation. The application of the Bomb model to Hela cells with AuNPs under 220 kVp X-ray irradiation indicated that a single ionization event for NPs caused by higher energy photons has a higher probability of killing a cell. NPs that are closer to the cell nucleus are more effective for radiosensitization. Microdosimetric calculations of the RBE for cell death of the Auger electron cascade cannot explain the experimentally observed radiosensitization by AGuIX or AuNP, while the proposed Bomb model is a potential candidate for describing NP-related radiosensitization at low NP concentrations.