Microdosimetry calculations in situ for clinically relevant photon sources and their correlation with the early DNA damage response
Bibliographic record
Abstract
Abstract Background Radiobiological data suggests variations in relative biological effectiveness (RBE) between clinically used photon‐based sources. A microdosimetric formalism using Monte Carlo (MC) methods can mechanistically describe the photon RBE. Experimentally derived RBE based on DNA double‐strand breaks () has been shown to scale with the microdosimetry quantity dose‐mean lineal energy (). Purpose To calculate microdosimetric spectra for clinically relevant photon sources, spanning from soft x‐rays produced by a 50 kVp x‐ray source through various brachytherapy sources up to a 6 MV medical linac. Furthermore, we investigated the correlation between and of different photon sources. Methods Photon sources simulated include low‐energy x‐rays (50 kVp), orthovoltage x‐rays (225 kVp), high‐dose‐rate brachytherapy sources ( 75 Se, 192 Ir and 60 Co), and a 6 MV medical linac. Secondary electron spectra at the cellular level were calculated for in vitro cell irradiation setups using Geant4 MC‐based packages, RapidBrachyMCTPS and RapidExternalBeam. The obtained spectra were used in MicroDose, a microdosimetry simulation software, to obtain microdosimetric quantities, including single‐event lineal energy () and specific energy () spectra, and dose‐mean and frequency‐mean quantities (, , , ). Uniform spherical targets (1–14 radius) and realistic HeLa and PC3 cell nucleus models were simulated using cell size data obtained from literature and nuclei size data from confocal microscopy imaging. Radiobiological experiments using foci quantified DNA double‐strand breaks for HeLa and PC3 cells after irradiations with 50 and 225 kVp, 192 Ir, and 6 MV linac, and was determined using 225 kVp as the reference. Results The calculated () is within the 3.5–1.2 keV/ range (1.8–0.2 keV/) for 1 simulated target size between the lowest energy 50 kVp x‐ray source and the highest energy 6 MV linac source, respectively. For the HeLa and PC3 cell nuclei models based on microscopy data, () spans from 1.6 to 0.6 keV/ (0.7 to 0.2 keV/). When compared between different target sizes, () ranges from 3.5 to 1.0 (1.8–0.4) keV/ between 1 and 10 radius targets for the 50 kVp x‐ray source. A smaller change is observed for 6 MV linac, ranging from 1.2 to 0.5 keV/ and 0.23 to 0.22 keV/ for and , respectively. For the simulated 75 Se source currently under investigation, the calculated values are 11%–24% higher relative to those of 192 Ir in the range of target sizes between 1 and 14 in radius. for HeLa cells was 1.40.7 for 50 kVp x‐rays, 0.50.2 for 192 Ir, and 0.70.4 for 6 MV linac irradiations. For PC3 cells, was 1.30.6, 0.80.4 and 0.50.3 for 50 kVp, 192 Ir and 6 MV linac, respectively. Measured values are consistent with ratios of the corresponding photon sources for HeLa and PC3 nucleus models. Conclusions Microdosimetric spectra strongly depend on the simulated energy of photon sources and target size, with and decreasing by a factor of 2–3 between diagnostic 50 kVp and 6 MV therapeutic x‐rays for target sizes from 1–14 in radius. The early damage indicates this stochastic change in energy density between various photon sources as the yields of foci per nucleus scale with of the source.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".