A Monte-Carlo-based study of a single-2D-detector proton-radiography system

PURPOSE: To assess the feasibility of a proton radiography (pRG) system based on a single thin pixelated detector for water-equivalent path length (WEPL) and relative stopping power (RSP) measurements.METHODS: A model of a pRG system consisting of a single pixelated detector measuring energy deposition and proton fluence was investigated in a Geant4-based Monte Carlo study. At the position directly after an object traversed by a broad proton beam, spatial 2D distributions are calculated of the energy deposition in, and the number of protons entering the detector. Their ratio relates to the 2D distribution of the average stopping power of protons in the detector. The system response is calibrated against the residual range in water of the protons to provide the 2D distribution of the WEPL of the object. The WEPL distribution is converted into the distribution of the RSP of the object. Simulations have been done, where the system has been tested on 13 samples of homogeneous materials of which the RSPs have been calculated and compared with RSPs determined from simulations of residual-range-in-water, which we refer to as reference RSPs.RESULTS: For both human-tissue- and non-human-tissue-equivalent materials, the RSPs derived with the detector agree with the reference values within 1%.CONCLUSION: The study shows that a pRG system based on one thin pixelated detection screen has the potential to provide RSP predictions with an accuracy of 1%.</p

Proton Radiography With Timepix Based Time Projection Chambers

The development of a proton radiography system to improve the imaging of patients in proton beam therapy is described. The system comprises gridpix based time projection chambers, which are based on the Timepix chip designed by the Medipix collaboration, for tracking the protons. This type of detector was chosen to have minimal impact on the actual determination of the proton tracks by the tracking detectors. To determine the residual energy of the protons, a BaF2 crystal with a photomultiplier tube is used. We present data taken in a feasibility experiment with phantoms that represent tissue equivalent materials found in the human body. The obtained experimental results show a good agreement with the performed simulations.</p

Real-Time PET Imaging for Range Verification of Helium Radiotherapy

Real-time range verification of particle beams is important for optimal exploitation of the tissue-sparing advantages of particle therapy. Positron Emission Tomography (PET) of the beam-induced positron emitters such as 15O (T1/2 = 122 s) and 11C (T1/2 = 1223 s) has been used for monitoring of therapy in both clinical and preclinical studies. However, the half-lives of these nuclides preclude prompt feedback, i.e., on a sub-second timescale, on dose delivery. The in vivo verification technique relying on the in-beam PET imaging of very short-lived positron emitters such as 12N (T1/2 = 11 ms), recently proposed and investigated in feasibility experiments with a proton beam, provides millimeter precision in range measurement a few tens of milliseconds after the start of an irradiation. With the increasing interest in helium therapy, it becomes relevant to study the feasibility of prompt feedback using PET also for helium beams. A recent study has demonstrated the production of very short-lived nuclides (T1/2 = 10 ms attributed to 12N and/or 13O) during irradiation of water and graphite with helium ions. This work is aimed at investigating the range verification potential of imaging these very short-lived nuclides. PMMA targets were irradiated with a 90 AMeV 4He pencil beam consisting of a series of pulses of 10 ms beam-on and 90 ms beam-off. Two modules of a modified Siemens Biograph mCT PET scanner (21 × 21 cm2), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. For the irradiation of PMMA, we identify the very short-lived activity earlier observed to be 12N (T1/2 = 11.0 ms). The range precision determined from the 12N activity profile that is measured after just one beam pulse was found to be 9.0 and 4.1 mm (1σ) with 1.3 × 1074He ions per pulse and 6.6 × 1074He ions per pulse, respectively. When considering 4.0 × 1074He ions, which is about the intensity of the most intense distal layer spot in a helium therapy plan, a range verification precision in PMMA of 5.7 mm (1σ) can be realized. The range precision scales approximately with the inverse square root of the number of 4He ions, i.e., the relative statistical accuracy of the number of coincidence events. Thus, when summing data over about 10 distal layer spots, this study shows good prospects for obtaining 1.8 mm (1σ) precision in range verification, within 50 ms after the start of a helium irradiation by in-beam PET imaging (scanner 29% solid angle) of 12N

A simple microscopy setup for visualizing cellular responses to DNA damage at particle accelerator facilities

Cellular responses to DNA double-strand breaks (DSBs) not only promote genomic integrity in healthy tissues, but also largely determine the efficacy of many DNA-damaging cancer treatments, including X-ray and particle therapies. A growing body of evidence suggests that activation of the mechanisms that detect, signal and repair DSBs may depend on the complexity of the initiating DNA lesions. Studies focusing on this, as well as on many other radiobiological questions, require reliable methods to induce DSBs of varying complexity, and to visualize the ensuing cellular responses. Accelerated particles of different energies and masses are exceptionally well suited for this task, due to the nature of their physical interactions with the intracellular environment, but visualizing cellular responses to particle-induced damage - especially in their early stages - at particle accelerator facilities, remains challenging. Here we describe a straightforward approach for real-time imaging of early response to particle-induced DNA damage. We rely on a transportable setup with an inverted fluorescence confocal microscope, tilted at a small angle relative to the particle beam, such that cells can be irradiated and imaged without any microscope or beamline modifications. Using this setup, we image and analyze the accumulation of fluorescently-tagged MDC1, RNF168 and 53BP1—key factors involved in DSB signalling—at DNA lesions induced by 254 MeV α-particles. Our results provide a demonstration of technical feasibility and reveal asynchronous initiation of accumulation of these proteins at different individual DSBs

Investigating the lateral dose response functions of point detectors in proton beams

Objective Point detector measurements in proton fields are perturbed by the volume effect originating from geometrical volume-averaging within the extended detector's sensitive volume and density perturbations by non-water equivalent detector components. Detector specific lateral dose response functions K(x) can be used to characterize the volume effect within the framework of a mathematical convolution model, where K(x) is the convolution kernel transforming the true dose profile D(x) into the measured signal profile of a detector M(x). The aim of this work is to investigate K(x) for detectors in proton beams. Approach The K(x) for five detectors were determined by iterative deconvolution of measurements of D(x) and M(x) profiles at 2 cm water equivalent depth of a narrow 150 MeV proton beam. Monte Carlo simulations were carried out for two selected detectors to investigate a potential energy dependence, and to study the contribution of volume-averaging and density perturbation to the volume effect. Main results The Monte Carlo simulated and experimentally determined K(x) agree within 2.1% of the maximum value. Further simulations demonstrate that the main contribution to the volume effect is volume-averaging. The results indicate that an energy or depth dependence of K(x) is almost negligible in proton beams. While the signal reduction from a Semiflex 3D ionization chamber in the center of a gaussian shaped field with 2 mm sigma is 32% for photons, it is 15% for protons. When measuring the field with a microDiamond the trend is less pronounced and reversed with a signal reduction for protons of 3.9% and photons of 1.9%. Significance The determined K(x) can be applied to characterize the influence of the volume effect on detectors measured signal profiles at all clinical proton energies and measurement depths. The functions can be used to derive the actual dose distribution from point detector measurements

Improving proton therapy by metal-containing nanoparticles:Nanoscale insights

The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/mu m) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (&gt;2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.</p

Radiation Hardness of dSiPM Sensors in a Proton Therapy Radiation Environment

In vivo verification of dose delivery in proton therapy by means of positron emission tomography (PET) or prompt gamma imaging is mostly based on fast scintillation detectors. The digital silicon photomultiplier (dSiPM) allows excellent scintillation detector timing properties and is thus being considered for such verification methods. We present here the results of the first investigation of radiation damage to dSiPM sensors in a proton therapy radiation environment. Radiation hardness experiments were performed at the AGOR cyclotron facility at the KVI-Center for Advanced Radiation Technology, University of Groningen. A 150-MeV proton beam was fully stopped in a water target. In the first experiment, bare dSiPM sensors were placed at 25 cm from the Bragg peak, perpendicular to the beam direction, a geometry typical for an in situ implementation of a PET or prompt gamma imaging device. In the second experiment, dSiPM-based PET detectors containing lutetium yttrium orthosilicate scintillator crystal arrays were placed at 2 and 4 m from the Bragg peak, perpendicular to the beam direction; resembling an in-room PET implementation. Furthermore, the experimental setup was simulated with a Geant4-based Monte Carlo code in order to determine the angular and energy distributions of the neutrons and to determine the 1-MeV equivalent neutron fluences delivered to the dSiPM sensors. A noticeable increase in dark count rate (DCR) after an irradiation with about 108 1-MeV equivalent neutrons/cm2 agrees with observations by others for analog SiPMs, indicating that the radiation damage occurs in the single photon avalanche diodes and not in the electronics integrated on the sensor chip. It was found that in the in situ location, the DCR becomes too large for successful operation after the equivalent of a few weeks of use in a proton therapy treatment room (about 5× 103 protons). For PET detectors in an in-room setup, detector performance was unchanged even after an irradiation equivalent to three years of use in a treatment room (3× 1015 protons)