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%.

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 functionsK(x) can be used to characterize the volume effect within the framework of a mathematical convolution model, whereK(x) is the convolution kernel transforming the true dose profileD(x) into the measured signal profile of a detectorM(x). The aim of this work is to investigateK(x) for detectors in proton beams.Approach. TheK(x) for five detectors were determined by iterative deconvolution of measurements ofD(x) andM(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 determinedK(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 ofK(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 determinedK(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.

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.

Feasibility of quasi-prompt PET-based range verification in proton therapy.

Compared to photon therapy, proton therapy allows a better conformation of the dose to the tumor volume with reduced radiation dose to co-irradiated tissues. In vivo verification techniques including positron emission tomography (PET) have been proposed as quality assurance tools to mitigate proton range uncertainties. Detection of differences between planned and actual dose delivery on a short timescale provides a fast trigger for corrective actions. Conventional PET-based imaging of 15O (T1/2 = 2 min) and 11C (T1/2 = 20 min) distributions precludes such immediate feedback. We here present a demonstration of near real-time range verification by means of PET imaging of 12N (T1/2 = 11 ms). PMMA and graphite targets were irradiated with a 150 MeV proton 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 each), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. The modifications enable the detectors to be switched off during the beam-on periods. 12N images were reconstructed using planar tomography. Using a 1D projection of the 2D reconstructed 12N image, the activity range was obtained from a fit of the activity profile with a sigmoid function. Range shifts due to modified target configurations were assessed for multiples of the clinically relevant 108 protons per pulse (approximately equal to the highest intensity spots in the pencil beam scanning delivery of a dose of 1 Gy over a cubic 1 l volume). The standard deviation of the activity range, determined from 30 datasets obtained from three irradiations on PMMA and graphite targets, was found to be 2.5 and 2.6 mm (1σ) with 108 protons per pulse and 0.9 and 0.8 mm (1σ) with 109 protons per pulse. Analytical extrapolation of the results from this study shows that using a scanner with a solid angle coverage of 57%, with optimized detector switching and spot delivery times much smaller than the 12N half-life, an activity range measurement precision of 2.0 mm (1σ) and 1.3 mm (1σ) within 50 ms into an irradiation with 4 × 107 and 108 protons per pencil beam spot can be potentially realized. Aggregated imaging of neighboring spots or, if possible, increasing the number of protons for a few probe beam spots will enable the realization of higher precision range measurement.

The production of positron emitters with millisecond half-life during helium beam radiotherapy.

Therapy with helium ions is currently receiving significantly increasing interest because helium ions have a sharper penumbra than protons and undergo less fragmentation than carbon ions and thus require less complicated dose calculations. For any ion of interest in hadron therapy, the accuracy of dose delivery is limited by range uncertainties. This has led to efforts by several groups to develop in vivo verification techniques, including positron emission tomography (PET), for monitoring of the dose delivery. Beam-on PET monitoring during proton therapy through the detection of short-lived positron emitters such as 12N (T 1/2 = 11 ms), an emerging PET technique, provides an attractive option given the achievable range accuracy, minimal susceptibility to biological washout and provision of near prompt feedback. Extension of this approach to helium ions requires information on the production yield of relevant short-lived positron emitters. This study presents the first measurements of the production of short-lived positron emitters in water, graphite, calcium and phosphorus targets irradiated with 59 MeV/u 3He and 50 MeV/u 4He beams. For these targets, the most produced short-lived nuclides are 13O/12N (T 1/2 = 8.6/11 ms) on water, 13O/12N on graphite, 43Ti/41Sc/42Sc (T 1/2 = 509-680 ms) on calcium, 28P (T 1/2 = 268 ms) on phosphorus. A translation of the results from elemental targets to PMMA and representative tissues such as adipose tissue, muscle, compact and cortical bone, shows the dominance of 13O/12N in at least the first 20 s of an irradiation with 4He and somewhat longer with 3He. As the production of 13O/12N in a 3He irradiation is 3-4 times higher than in a 4He irradiation, from a statistical point of view, range verification using 13O/12N PET imaging will be about 2 times more precise for a 3He irradiation compared to a 4He irradiation.

Quantitative comparison of commercial and non-commercial metal artifact reduction techniques in computed tomography.

OBJECTIVES: Typical streak artifacts known as metal artifacts occur in the presence of strongly attenuating materials in computed tomography (CT). Recently, vendors have started offering metal artifact reduction (MAR) techniques. In addition, a MAR technique called the metal deletion technique (MDT) is freely available and able to reduce metal artifacts using reconstructed images. Although a comparison of the MDT to other MAR techniques exists, a comparison of commercially available MAR techniques is lacking. The aim of this study was therefore to quantify the difference in effectiveness of the currently available MAR techniques of different scanners and the MDT technique. MATERIALS AND METHODS: Three vendors were asked to use their preferential CT scanner for applying their MAR techniques. The scans were performed on a Philips Brilliance ICT 256 (S1), a GE Discovery CT 750 HD (S2) and a Siemens Somatom Definition AS Open (S3). The scans were made using an anthropomorphic head and neck phantom (Kyoto Kagaku, Japan). Three amalgam dental implants were constructed and inserted between the phantom's teeth. The average absolute error (AAE) was calculated for all reconstructions in the proximity of the amalgam implants. RESULTS: The commercial techniques reduced the AAE by 22.0±1.6%, 16.2±2.6% and 3.3±0.7% for S1 to S3 respectively. After applying the MDT to uncorrected scans of each scanner the AAE was reduced by 26.1±2.3%, 27.9±1.0% and 28.8±0.5% respectively. The difference in efficiency between the commercial techniques and the MDT was statistically significant for S2 (p=0.004) and S3 (p<0.001), but not for S1 (p=0.63). CONCLUSIONS: The effectiveness of MAR differs between vendors. S1 performed slightly better than S2 and both performed better than S3. Furthermore, for our phantom and outcome measure the MDT was more effective than the commercial MAR technique on all scanners.

Relative electron density determination using a physics based parameterization of photon interactions in medical DECT.

Radiotherapy and particle therapy treatment planning require accurate knowledge of the electron density and elemental composition of the tissues in the beam path to predict the local dose deposition. We describe a method for the analysis of dual energy computed tomography (DECT) images that provides the electron densities and effective atomic numbers of tissues. The CT measurement process is modelled by system weighting functions, which apply an energy dependent weighting to the parameterization of the total cross section for photon interactions with matter. This detailed parameterization is based on the theoretical analysis of Jackson and Hawkes and deviates, at most, 0.3% from the tabulated NIST values for the elements H to Zn. To account for beam hardening in the object as present in the CT image we implemented an iterative process employing a local weighting function, derived from the method proposed by Heismann and Balda. With this method effective atomic numbers between 1 and 30 can be determined. The method has been experimentally validated on a commercially available tissue characterization phantom with 16 inserts made of tissue substitutes and aluminium that has been scanned on a dual source CT system with tube potentials of 100 kV and 140 kV using a clinical scan protocol. Relative electron densities of all tissue substitutes have been determined with accuracy better than 1%. The presented DECT analysis method thus provides high accuracy electron densities and effective atomic numbers for radiotherapy and especially particle therapy treatment planning.