Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

Electron contamination suppression in transmission detectors for radiotherapy.

Objective.Higher energy and intensity radiotherapy beams are being used, in part, due to the increased spatial accuracy of treatments. However, higher intensity beams can result in a larger total dose error, motivating the increasing need for real-time dose monitoring. We are developing a thin, real-time upstream monolithic active pixel sensor based system for beam monitoring with excellent precision on measuring the beam shape. Here we present a method to additionally provide dosimetry by adding thin conversion material in strips to the surface of the detector, a grating structure.Approach.By modulating the thickness of the conversion material to minimally disturb the contamination electron signal while enhancing the photon signal, the difference in these signals can be used to extract a photon-only signal, and hence dose. The simulation software Gate, based on Geant4, is utilised to study whether well functioning gratings can be better made from aluminium or copper and to optimise the thickness of a copper grating.Main results.It is possible to enhance the photon signal by a factor 6.7 (7.7) compared to the bare sensor for a 5.8 (6.7) MV beam, without modulation of the signal due to beam electrons.Significance.The grating can be used to perform dosimetry in real-time using a thin upstream detector.

In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment.

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.

Suitability of Athena Monolithic Active Pixel Sensor for upstream monitoring of 6 MV, 6 FFF and 10 MV treatments.

We are developing a thin, real-time radiotherapy verification sensor based on the Athena, a large-scale MAPS. The goal in radiotherapy verification is to measure the multileaf collimator positions and beam intensity to ensure the accuracy and safety of treatment delivery. Previously, results on this have been published. In this paper, we present results that clearly demonstrate that the Athena does not saturate, even at the highest beam intensities in a 6 FFF 10 × 10 cm2 field and thus is suitable for clinical deployment.

Performance of a Full-Scale Upstream MAPS-Based Verification Device for Radiotherapy.

Intensity-modulated radiotherapy is a widely used technique for accurately targeting cancerous tumours in difficult locations using dynamically shaped beams. This is ideally accompanied by real-time independent verification. Monolithic active pixel sensors are a viable candidate for providing upstream beam monitoring during treatment. We have already demonstrated that a Monolithic Active Pixel Sensor (MAPS)-based system can fulfill all clinical requirements except for the minimum required size. Here, we report the performance of a large-scale demonstrator system consisting of a matrix of 2 × 2 sensors, which is large enough to cover almost all radiotherapy treatment fields when affixed to the shadow tray of the LINAC head. When building a matrix structure, a small dead area is inevitable. Here, we report that with a newly developed position algorithm, leaf positions can be reconstructed over the entire range with a position resolution of below ∼200 µm in the centre of the sensor, which worsens to just below 300 µm in the middle of the gap between two sensors. A leaf position resolution below 300 µm results in a dose error below 2%, which is good enough for clinical deployment.

Simulation and Optimization Studies of the LHCb Beetle Readout ASIC and Machine Learning Approach for Pulse Shape Reconstruction.

The optimization of the Beetle readout ASIC and the performance of the software for the signal processing based on machine learning methods are presented. The Beetle readout chip was developed for the LHCb (Large Hadron Collider beauty) tracking detectors and was used in the VELO (Vertex Locator) during Run 1 and 2 of LHC data taking. The VELO, surrounding the LHC beam crossing region, was a leading part of the LHCb tracking system. The Beetle chip was used to read out the signal from silicon microstrips, integrating and amplifying it. The studies presented in this paper cover the optimization of its electronic configuration to achieve the lower power consumption footprint and the lower operational temperature of the sensors, while maintaining a good condition of the analogue response of the whole chip. The studies have shown that optimizing the operational temperature is possible and can be beneficial when the detector is highly irradiated. Even a single degree drop in silicon temperature can result in a significant reduction in the leakage current. Similar studies are being performed for the future silicon tracker, the Upstream Tracker (UT), which will start operating at LHC in 2021. It is expected that the inner part of the UT detector will suffer radiation damage similar to the most irradiated VELO sensors in Run 2. In the course of analysis we also developed a general approach for the pulse shape reconstruction using an ANN approach. This technique can be reused in case of any type of front-end readout chip.

Effect of Commercial Off-The-Shelf MAPS on γ-Ray Ionizing Radiation Response to Different Integration Times and Gains.

We report the γ-ray ionizing radiation response of commercial off-the-shelf (COTS) monolithic active-pixel sensors (MAPS) with different integration times and gains. The distribution of the eight-bit two-dimensional matrix of MAPS output frame images was studied for different parameter settings and dose rates. We present the first results of the effects of these parameters on the response of the sensor and establish a linear relationship between the average response signal and radiation dose rate in the high-dose rate range. The results show that the distribution curves can be separated into three ranges. The first range is from 0 to 24, which generates the first significant low signal peak. The second range is from 25 to 250, which shows a smooth gradient change with different integration times, gains, and dose rates. The third range is from 251 to 255, where a final peak appears, which has a relationship with integral time, gain, and dose rate. The mean pixel value shows a linear dependence on the radiation dose rate, albeit with different calibration constants depending on the integration time and gain. Hence, MAPS can be used as a radiation monitoring device with good precision.