HollandPTC is an independent outpatient center for proton therapy, scientific research, and education. Patients with different types of cancer are treated with Intensity Modulated Proton Therapy (IMPT). Additionally, the HollandPTC R&D consortium conducts scientific research into the added value and improvements of proton therapy. To this end, HollandPTC created clinical and pre-clinical research facilities including a versatile R&D proton beamline for various types of biologically and technologically oriented research. In this work, we present the characterization of the R&D proton beamline of HollandPTC. Its pencil beam mimics the one used for clinical IMPT, with energy ranging from 70 up to 240 MeV, which has been characterized in terms of shape, size, and intensity. For experiments that need a uniform field in depth and lateral directions, a dual ring passive scattering system has been designed, built, and characterized. With this system, field sizes between 2 × 2 cm² and 20 × 20 cm² with 98 % uniformity are produced with dose rates ranging from 0.5 Gy/min up to 9 Gy/min. The unique and customized support of the dual ring system allows switching between a pencil beam and a large field in a very simple and fast way, making the HollandPTC R&D proton beam able to support a wide range of different applications.

A Geant4 based simulation platform of the Holland Proton Therapy Centre (HollandPTC, Netherlands) R&D beamline (G4HPTC-R&D) was developed to enable the planning, optimisation and advanced dosimetry for radiobiological studies. It implemented a six parameter non-symmetrical Gaussian pencil beam surrogate model to simulate the R&D beamline in both a pencil beam and passively scattered field configuration. Three different experimental proton datasets (70 MeV, 150 MeV, and 240 MeV) of the pencil beam envelope evolution in free air and depth-dose profiles in water were used to develop a set of individual parameter surrogate functions to enable the modelling of the non-symmetrical Gaussian pencil beam properties with only the ProBeam isochronous cyclotron mean extraction proton energy as input. This refined beam model was then benchmarked with respect to three independent experimental datasets of the R&D beamline operating in both a pencil beam configuration at 120 and 200 MeV, and passively scattered field configuration at 150 MeV. It was shown that the G4HPTC-R&D simulation platform can reproduce the pencil beam envelope evolution in free air and depth-dose profiles to within an accuracy on the order of ±5% for all tested energies, and that it was able to reproduce the 150 MeV passively scattered field to the specifications need for clinical and radiobiological applications.

Purpose: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. Methods: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. Results: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. Conclusion: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Background: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. Aims: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. Materials and Methods: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. Results: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. Discussion: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. Conclusion: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Over the last decade one of the most significant technological advances made in the field of radiation detectors for nuclear medicine was the development of Silicon Photomultipler (SiPM) sensors. At present only a small number of SiPM based radiation detectors for Single Photon Emission Computed Tomography (SPECT) applications have been explored, and even fewer experimental prototypes developed. An in-silico investigation into the optimal design of a Philips DPC3200 SiPM photosensor-based thin monolithic scintillator detector for SPECT applications was undertaken using the Monte Carlo radiation transport modelling toolkit Geant4 version 10.5. The performance of the 20 different SPECT radiation detector configurations, 4 scintillator materials (NaI(Tl), GAGG(Ce), CsI(Tl) and LaBr₃(Ce)) and 5 thicknesses (1–5 mm), were determined through the use of seven figures of merit. It was found that a crystal thickness range of 4–5 mm was required for all four materials to ensure acceptable energy resolution, sensitivity and spatial resolution performance with the Philips DPC3200 SiPM. Any thinner than this and the performance of all four materials was found to degrade rapidly due to a high probability of material specific fluorescence x-ray escape after incident gamma/x-ray photoelectric absorption. When factoring in each material's magnetic resonance imaging compatibility, hygroscopy, and cost, it was found that CsI(Tl) represents the most promising material to construct tileable Philips digital SiPM based thin monolithic scintillator detectors for SPECT applications.

The production, application, and/or measurement of polarised X-/gamma rays are key to the fields of synchrotron science and X-/gamma-ray astronomy. The design, development and optimisation of experimental equipment utilised in these fields typically relies on the use of Monte Carlo radiation transport modelling toolkits such as Geant4. In this work the Geant4 “G4LowEPPhysics” electromagnetic physics constructor has been reconfigured to offer a best set of electromagnetic physics models for studies exploring the transport of low energy polarised X-/gamma rays. An overview of the physics models implemented in “G4LowEPPhysics”, and it's experimental validation against Compton X-ray polarimetry measurements of the BL38B1 beamline at the SPring-8 synchrotron (Sayo, Japan) is reported. “G4LowEPPhysics” is shown to be able to reproduce the experimental results obtained at the BL38B1 beamline (SPring-8) to within a level of accuracy on the same order as Geant4’s X-/gamma ray interaction cross-sectional data uncertainty (approximately ± 5 %).

Low-cost muon detectors utilising cheap plastic scintillators and a limited number of individual silicon photomultipliers (SiPMs) offer a compelling approach to cheap experimental designs, provided the event localisation of a traversing particle can be accurately determined. In this theoretical work, we use Geant4 to simulate a diverse range of detector configurations, shapes and SiPM photosensors, predicting the light intensity received at a given SiPM. Testing a range of methods to localise muon events we determine that machine learning techniques outperform analytic models, and of these, a simple gradient boosted framework is the most reliably accurate localisation technique for our simulated scintillators. We find that a simple square scintillator outperforms other geometries and that AI performs, when applied to this shape, with a linear relationship between the positional accuracy of the event recovery and the average distance between photosensors around the detector perimeter.

Organ-specific, targeted field-of-view (FoV) positron emission tomography (PET)/magnetic resonance imaging (MRI) inserts are viable solutions for a number of imaging tasks where whole-body PET/MRI systems lack the necessary sensitivity and resolution. To meet the required PET detector performance of these systems, high count-rates and effective spatial resolutions on the order of a few mm, a novel two-axis patterned reflector foil pixelated scintillator crystal array design is developed and its proof-of-concept illustrated in-silico with the Monte Carlo radiation transport modeling toolkit Geant4. It is shown that the crystal surface roughness and phased open reflector cross-sectional patterns could be optimized to maximize either the PET radiation detector's effective spatial resolution, or count rate before event pile up. In addition, it was illustrated that these two parameters had minimal impact on the energy and time resolution of the proposed PET radiation detector design. Finally, it is shown that a PET radiation detector with balance performance could be constructed using ground crystals and phased open reflector cross-sectional pattern corresponding to the middle of the tested range.

The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage – radiobiology, radiation physics, radiation protection and, in particular, medical physics – requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC) simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs) and double strand breaks (DSBs) in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path.). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.

We extended a generic Geant4 application for mechanistic DNA damage simulations to an Escherichia coli cell geometry, finding electron damage yields and proton damage yields largely in line with experimental results. Depending on the simulation of radical scavenging, electrons double strand breaks (DSBs) yields range from 0.004 to 0.010 DSB Gy⁻¹ Mbp⁻¹, while protons have yields ranging from 0.004 DSB Gy⁻¹ Mbp⁻¹ at low LETs and with strict assumptions concerning scavenging, up to 0.020 DSB Gy⁻¹ Mbp⁻¹ at high LETs and when scavenging is weakest. Mechanistic DNA damage simulations can provide important limits on the extent to which physical processes can impact biology in low background experiments. We demonstrate the utility of these studies for low dose radiation biology calculating that in E. coli, the median rate at which the radiation background induces double strand breaks is 2.8 × 10⁻⁸ DSB day⁻¹, significantly less than the mutation rate per generation measured in E. coli, which is on the order of 10⁻³.

A novel treatment planning framework, the Relative Biological Effective Dose (RBED), for high Z nanoparticle (NP)-enhanced photon radiotherapy is developed and tested in silico for the medical exemplar of neoadjuvant (preoperative) breast cancer MV photon radiotherapy. Two different treatment scenarios, conventional and high Z NP enhanced, were explored with a custom Geant4 application that was developed to emulate the administration of a single 2 Gy fraction as part of a 50 Gy radiotherapy treatment plan. It was illustrated that there was less than a 1% difference in the dose deposition throughout the standard and high Z NP-doped adult female phantom. Application of the RBED framework found that the extent of possible biological response with high Z NP doping was great than expected via the dose deposition alone. It is anticipated that this framework will assist the scientific community in future high Z NP-enhanced in-silico, pre-clinical and clinical trials.

Absolute measurements of the radiolytic yield of Fe3+ in a ferrous sulphate dosimeter formulation (6 mM Fe2+), with a 20 keV x-ray monoenergetic beam, are reported. Dose-rate suppression of the radiolytic yield was observed at dose rates lower than and different in nature to those previously reported with x-rays. We present evidence that this effect is most likely to be due to recombination of free radicals radiolytically produced from water. The method used to make these measurements is also new and it provides radiolytic yields which are directly traceable to the SI standards system. The data presented provides new and exacting tests of radiation chemistry codes.

Mechanistic modelling of DNA damage in Monte Carlo simulations is highly sensitive to the parameters that define DNA damage. In this work, we use a simple testing geometry to investigate how different choices of physics models and damage model parameters can change the estimation of DNA damage in a mechanistic DNA damage simulation built in Geant4-DNA. The choice of physics model can lead to variations by up to a factor of two in the yield of physically induced strand breaks, and the parameters that determine scavenging, and physical and chemical single strand break induction can have even larger consequences. Using low energy electrons as primary particles, a variety of parameters are tested in this geometry in order to arrive at a parameter set consistent with past simulation studies. We find that the modelling of scavenging can play an important role in determining results, and speculate that high-scavenging regimes, where only chemical radicals within 1 nm of DNA are simulated, could provide a good means of testing mechanistic DNA simulations.

We report on the recent progress within the Geant4 electromagnetic physics subpackages. Several new interfaces and models recently introduced are already used in LHC applications and may be useful for any type of simulation. Significant developments were carried out to improve the user interface, develop models of single and multiple scattering, and validate high energy models. Part of these developments are included in the Geant4 10.2 release and the full set are available in the new version 10.3 of December, 2016.