Ultra-high dose rate (UHDR) irradiation regimes have the potential to spare normal tissue while keeping equivalent tumoricidal capacity than conventional dose rate radiotherapy (CONV-RT). This has been called the FLASH effect. In this work, we present a new simulation framework aiming to study the production of radical species in water and biological media under different irradiation patterns. The chemical stage (heterogeneous phase) is based on a nonlinear reaction-diffusion model, implemented in GPU. After the first 1 μs, no further radical diffusion is assumed, and radical evolution may be simulated over long periods of hundreds of seconds. Our approach was first validated against previous results in the literature and then employed to assess the influence of different temporal microstructures of dose deposition in the expected biological damage. The variation of the Normal Tissue Complication Probability (NTCP), assuming the model of Labarbe et al., where the integral of the peroxyl radical concentration over time (AUC-ROO) is taken as surrogate for biological damage, is presented for different intra-pulse dose rate and pulse frequency configurations, relevant in the clinical scenario. These simulations yield that overall, mean dose rate and the dose per pulse are the best predictors of biological effects at UHDR.

Objective. The GPU-based Ultra-fast Monte Carlo positron emission tomography simulator (UMC-PET) incorporates the physics of the emission, transport and detection of radiation in PET scanners. It includes positron range, non-colinearity, scatter and attenuation, as well as detector response. The objective of this work is to present and validate UMC-PET as a a multi-purpose, accurate, fast and flexible PET simulator. Approach. We compared UMC-PET against PeneloPET, a well-validated MC PET simulator, both in preclinical and clinical scenarios. Different phantoms for scatter fraction (SF) assessment following NEMA protocols were simulated in a 6R-SuperArgus and a Biograph mMR scanner, comparing energy histograms, NEMA SF, and sensitivity for different energy windows. A comparison with real data reported in the literature on the Biograph scanner is also shown. Main results. NEMA SF and sensitivity estimated by UMC-PET where within few percent of PeneloPET predictions. The discrepancies can be attributed to small differences in the physics modeling. Running in a 11 GB GeForce RTX 2080 Ti GPU, UMC-PET is ∼1500 to ∼2000 times faster than PeneloPET executing in a single core Intel(R) Xeon(R) CPU W-2155 @ 3.30 GHz. Significance. UMC-PET employs a voxelized scheme for the scanner, patient adjacent objects (such as shieldings or the patient bed), and the activity distribution. This makes UMC-PET extremely flexible. Its high simulation speed allows applications such as MC scatter correction, faster SRM estimation for complex scanners, or even MC iterative image reconstruction.

Background: Proton therapy allows for better localization of the dose distribution in the tumor. In addition, the FLASH effect can be exploited to reduce the toxicity to healthy tissue by using short‐pulsed treatment at ultra‐high dose rates (UHDR). Such intense radiation conditions have limited options for active detectors for dosimetry. Purpose: Silicon carbide‐based diodes are proposed as a cost‐effective alternative to diamond detectors for dosimetry in UHDR. Methods: Two new SiC diodes designed and fabricated at the Institute of Microelectronics of Barcelona (IMB‐CNM) were exposed to 20 proton low‐energy pulses with up to 25 Gy per pulse to verify the capability of this technology to function under UHDR radiation at the Center for Microanalysis of Materials (CMAM) facility. The response of a single diode was correlated to the dose per pulse measured with calibrated EBT4 radiochromic films. Likewise, a 2 2 dosimeter matrix mounted on a motorized stage system was used as a proof‐of‐concept for a large array dose monitor under construction, by scanning the response of each of its pixels as a function of position with respect to the beam, compared against calibrated radiochromic films. Finally, the same device was exposed to varying pulse lengths, while connected to a current‐to‐voltage amplifier and an oscilloscope in order to measure the pulse structure. Results: First, the single diode showed a good dose rate linearity. No indication of saturation was observed even at the highest dose per pulse (DPP) of 25 Gy. This was observed even after over‐exposure of 52 kGy of 7 MeV protons, although its response lowered to 31% of the initially measured value. Second, the beam profiles observed by the pixelated detector were consistent with those of the reference measurements. Finally, the full width half maximums of the pulses observed by the pixels show good correlation with the pulse width of the beam. Conclusions: The SiC detectors developed at IMB‐CNM were able to withstand and accurately measure the dose under FLASH compatible beam characteristics, even in the case of low‐energy protons (7 MeV). The pixelated device showed promising results for a full array monitor for quality assurance, and the capability of time‐resolved pulse measurements, the latter after optimization of the electronics.

Objective. Clinical implementation of in-beam positron emission tomography (PET) monitoring in proton therapy (PT) requires the integration of an online fast and reliable dose calculation engine. This manuscript reports on the achievement of real-time reconstruction of 3D dose and activity maps with proton range verification from experimental in-beam PET measurements. Approach. Several cylindrical homogeneous PMMA phantoms were irradiated with a monoenergetic 70 MeV proton beam in a clinical facility. Additionally, PMMA range-shifting foils of varying thicknesses were placed at the proximal surface of the phantom to investigate range shift prediction capabilities. PET activity was measured using a state-of-the-art in-house developed six-module PET scanner equipped with online PET reconstruction capabilities. For real-time dose estimation, we integrated this system with an in-beam dose estimation algorithm, which combines a graphical processing unit-based 3D reconstruction algorithm with a dictionary-based software, capable of estimating deposited doses from the 3D PET activity images. The range shift prediction performance has been quantitatively studied in terms of the minimum dose to be delivered and the maximum acquisition time. Main results. With this framework, 3D dose maps were accurately reconstructed and displayed with a delay as short as one second. For a dose fraction of 8.4 Gy at the Bragg peak maximum, range shifts as small as 1 mm could be detected. The quantitative analysis shows that accumulating 20 s of statistics from the start of the irradiation, doses down to 1 Gy could be estimated online with total uncertainties smaller than 2 mm. Significance. The hardware and software combination employed in this work can deliver dose maps and accurately predict range shifts after short acquisition times and small doses, suggesting that real-time monitoring and dose reconstruction during PT are within reach. Future work will focus on testing the methodology in more complex clinical scenarios and on upgrading the PET prototype for increased sensitivity.