Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals

Yan Zhang; Chenyang Huang; Ankang Hu; Yucheng Wang; Wanyi Zhou; Jiaqi Qiu; Jian Wang; Qibin Fu; Tuchen Huang; Hao Zha; Wei Wang; Xiaowu Deng; Junli Li

arXiv · 2411.19194

Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals

Yan Zhang·Chenyang Huang·Ankang Hu·Yucheng Wang·Wanyi Zhou·Jiaqi Qiu·Jian Wang·Qibin Fu·Tuchen Huang·Hao Zha·Wei Wang·Xiaowu Deng·Junli Li

View original source ↗Read source document ↗Export metadata ↓

Abstract

Purpose: Our aim was to elucidate the critical factors responsible for inducing the FLASH effect, focusing on the role of free radicals through simulation and experimental approaches. Methods and Materials: The whole abdomen of C57BL/6 mice was irradiated with 6 MeV electron beam. The endpoint was acute intestinal toxicity quantified by histological score. Total doses ranging from 6 to 15 Gy were evaluated. The impact of the mean dose rate (MDR) was assessed in the range of 40 to 900 Gy/s. Dose per pulse (DPP) of 0.5 Gy and 3 Gy were compared. The recombination of peroxyl radicals were simulated. Further comparisons were conducted by incorporating the antioxidant amifostine. Results: When varying total doses with a constant MDR of 900 Gy/s, the FLASH effect was not observed until the dose reached 15 Gy. For a total dose of 15 Gy and varying MDR, the FLASH effect was observed only when MDR reached 100 Gy/s. For a dose of 15 Gy and an MDR of 150 Gy/s, no significant difference in biological effect was observed between low DPP and high DPP. The simulation results indicated that the fraction of peroxyl radicals recombination remained nearly zero at conventional dose rates. For FLASH irradiation, the recombination fraction increased linearly with the dose. Notably, the dose delivery time corresponding to 50% change in the recombination fraction was approximately 300 ms. The addition of amifostine effectively eliminated the difference between FLASH group and CONV group. Conclusions: The critical requirement for observing the sparing effect at the biological endpoint is the administration of an adequate dose within the time window of the radical reaction. Additionally, the important role of free radical was verified after introducing antioxidants, suggesting that the generation and recombination of free radicals are pivotal factors influencing the FLASH sparing effect.

Explore related subjects

physics.med-ph

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Yan Zhang, Chenyang Huang, Ankang Hu, Yucheng Wang, Wanyi Zhou, Jiaqi Qiu, Jian Wang, Qibin Fu, Tuchen Huang, Hao Zha, Wei Wang, Xiaowu Deng, Junli Li. 2024-11-28. Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals. https://arxiv.org/abs/2411.19194

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Phase-contrast micro-CT for intra-operative breast tumour margin assessment using a microfocus x-ray source and photon-counting detector

Objective: Intra-operative tumour margin assessment during breast-conserving surgery requires rapid, high-resolution imaging of excised tissue, allowing the surgical team to take appropriate action within a single operation. This study evaluates a custom propagation-based phase-contrast micro-computed tomography (micro-CT) system designed to meet these clinical constraints without specialised optical elements. Methods: The experimental setup pairs a microfocus x-ray source with a photon-counting detector in a cone-beam geometry. We explore how the spatial coherence of the source can provide propagation-based phase contrast -- with no additional specialised optical elements -- and balance this against maximising the x-ray flux of the cone-beam geometry. System performance was evaluated across two anode target materials and filtration configurations at various tube power settings. Imaging capabilities were validated using anthropomorphic breast tissue phantoms and a formalin-fixed paraffin-embedded (FFPE) breast tissue specimen, with reconstructions compared against gold-standard histology. Results: An unfiltered tungsten target operated at 40 kVp yielded optimal image quality. The optimised system achieved high-resolution CT reconstructions of a 5 cm diameter sample with an isotropic voxel size of 40.7 $\upmu\text{m}$ in a scan time of 12 minutes. Reconstructed volumes demonstrated strong visual correlation with corresponding histology slides. Conclusion: Combining a microfocus source with a photon-counting detector enables high-resolution, phase-contrast micro-CT within a clinically viable timeframe, demonstrating strong potential for intra-operative margin assessment.

physics.med-ph↗

arXiv2026

Understanding Search and Decision Errors in Liver Metastasis Detection and the Effects of Lower Radiation Dose

The detection performance of liver metastases decreases with the reduction of radiation dose, but misses are heterogeneous. Previous eye tracking work has characterized missed metastases into two categories: search errors i.e., the eyes never land on the lesion, and decision errors i.e., the lesion is seen but not recognized as malignant. We integrated three prior reader studies to answer this question. In all studies, radiologists interpreted the same set of 40 contrast enhanced abdominal CT exams containing 91 liver metastases whose locations had been previously marked. In two studies, the workstation recorded their gaze and eye movements. Using eye dwell times, metastases were classified as search-error-dominant (majority of misses had <2 sec gaze time) or decision-error-dominant (>2 sec gaze time). In the third study, exams were interpreted both at 120 and 200 quality reference mAs (QRM) by ten radiologists. The third study did not include eye tracking. Out of 91 liver metastases, we excluded 16 that were never missed in the eye tracking studies and used 75 liver metastases for the present study.

physics.med-ph↗

arXiv2026

Develop and Optimize 5DCT Imaging Simulation and Reconstruction Methods

Purpose: To develop and optimize a 5DCT (3D + cardiac phase + respiratory phase) imaging simulation and reconstruction pipeline, and to compare two sinogram-space interpolation methods for reconstructing images at arbitrary combinations of cardiac and respiratory phase. Methods: Helical CT projections were simulated from the 4D XCAT phantom across a range of cardiac and respiratory motion states, with Poisson and electronic noise added. Ground-truth-matched volumes were generated at 5 cardiac phases and 10 respiratory amplitudes (50 total phase combinations). Because acquired projections are sparsely and unevenly distributed across this joint phase space, each target slice was reconstructed by interpolating rebinned sinogram rows to the target cardiac phase and respiratory amplitude, using either 2D scattered barycentric interpolation or 2D scattered local linear interpolation with a circular kernel for cardiac phase. Reconstructed volumes were compared to phantom ground truth using mean absolute error (MAE), and to conventional respiratory-gated 4DCT (r4DCT) reconstructed from the same simulated data. Results: Both interpolation methods eliminated the severe axial misalignment artifacts present when helical projections were reconstructed without phase-space interpolation. Local linear interpolation achieved lower MAE than barycentric interpolation across most tested conditions, with the largest improvement at low pitch. The 5DCT pipeline also produced respiratory-only volumes with fewer residual cardiac-motion artifacts than conventional r4DCT reconstructed from the same projection data, including at standard clinical pitch (0.1). Conclusions: 5DCT reconstruction using sinogram-space interpolation is feasible and can jointly resolve cardiac and respiratory motion with better accuracy than conventional 4DCT reconstruction.

physics.med-ph↗