Analytical modeling and Monte Carlo simulations of multi-parallel slit and knife-edge slit prompt gamma cameras.

Purpose.Present and validate an analytical model (AM) to calculate efficiency and spatial resolution of multi-parallel slit (MPS) and knife-edge slit (KES) cameras in the context of prompt gamma (PG) imaging in proton therapy, as well as perform a fair comparison between two prototypes of these cameras with their design specifications.Materials and methods.Monte Carlo (MC) simulations with perfect (ideal) conditions were performed to validate the proposed AM, as well as simulations in realistic conditions for the comparison of both prototypes. The spatial resolution obtained from simulations was derived from reconstructed PG profiles. The falloff retrieval precision (FRP) was quantified based on the variability of PG profiles from 50 different realizations.Results.The AM shows that KES and MPS designs fulfilling 'MPS-KES similar conditions' should have very close actual performances if the KES slit width corresponds to the half of the MPS slit width. Reconstructed PG profiles from simulated data with both cameras were used to compute the efficiency and spatial resolutions to compare against the model predictions. The FRP of both cameras was calculated with realistic detection conditions for beams with 107, 108and 109incident protons. A good agreement was found between the values predicted by the AM and those obtained from MC simulations (relative deviations of the order of 5%).Conclusion.The MPS camera outperforms the KES camera with their design specifications in realistic conditions and both systems can reach millimetric precision in the determination of the falloff position with 108or more initial protons.

Imaging issues specific to hadrontherapy (proton, carbon, helium therapy and other charged particles) for radiotherapy planning, setup, dose monitoring and tissue response assessment.

Imaging is critical to each step of precision radiation therapy, i.e. planning, setup, delivery and assessment of response. Hadrontherapy can be considered to deliver more precise dose distribution that may better spare normal tissues from intermediate low doses of radiation. In addition, hadrontherapy using high linear energy transfer ions may also be used for dose escalation on biological target volumes defined by functional imaging. However, the physical characteristics of hadrontherapy also make it more demanding in terms of imaging accuracy and image-based dose calculation. Some of the developments needed in imaging are specific to hadrontherapy. The current review addresses current status of imaging in proton therapy and the drawbacks of photon-based imaging for hadrons. It also addresses requirements in hadrontherapy planning with respect to multimodal imaging for proper target and organ at risk definition as well as to target putative radioresistant areas such as hypoxic ones, and with respect to dose calculation using dual energy CT, MR-proton therapy, proton radiography. Imaging modalities, such as those used in photon-based radiotherapy (intensity modulated and stereotactic radiotherapy), are somewhat already implemented or should be reaching "routine" hadrontherapy (at least proton therapy) practice in planning, repositioning and response evaluation optimizable within the next five years. Online monitoring imaging by PET, as currently developed for hadrontherapy, is already available. Its spatiotemporal limits restrict its use but similar to prompt gamma detection, represents an area of active research for the next 5 to 10 years. Because of the more demanding and specific dose deposit characteristics, developments image-guided hadrontherapy, such as specific proton imaging using tomography or ionoacoustics, as well as delivery with MR-proton therapy, may take another 10 years to reach the clinics in specific applications. Other aspects are briefly described such as range monitoring. Finally, the potential of imaging normal tissue changes and challenges to assess tumour response are discussed.

Ultra-fast prompt gamma detection in single proton counting regime for range monitoring in particle therapy.

In order to fully exploit the ballistic potential of particle therapy, we propose an online range monitoring concept based on time-of-flight (TOF)-resolved prompt gamma (PG) detection in a single proton counting regime. In a proof of principle experiment, different types of monolithic scintillating gamma detectors are read in time coincidence with a diamond-based beam hodoscope, in order to build TOF spectra of PG generated in a target presenting an air cavity of variable thickness. Since the measurement was carried out at low beam currents (< 1 proton/bunch) it was possible to reach excellent coincidence time resolutions, of the order of 100 ps (σ). Our goal is to detect possible deviations of the proton range with respect to treatment planning within a few intense irradiation spots at the beginning of the session and then carry on the treatment at standard beam currents. The measurements were limited to 10 mm proton range shift. A Monte Carlo simulation study reproducing the experiment has shown that a 3 mm shift can be detected at 2σ by a single detector of ∼1.4 × 10-3 absolute detection efficiency within a single irradiation spot (∼108 protons) and an optimised experimental set-up.

CCMod: a GATE module for Compton camera imaging simulation.

Compton cameras are gamma-ray imaging systems which have been proposed for a wide variety of applications such as medical imaging, nuclear decommissioning or homeland security. In the design and optimization of such a system Monte Carlo simulations play an essential role. In this work, we propose a generic module to perform Monte Carlo simulations and analyses of Compton Camera imaging which is included in the open-source GATE/Geant4 platform. Several digitization stages have been implemented within the module to mimic the performance of the most commonly employed detectors (e.g. monolithic blocks, pixelated scintillator crystals, strip detectors...). Time coincidence sorter and sequence coincidence reconstruction are also available in order to aim at providing modules to facilitate the comparison and reproduction of the data taken with different prototypes. All processing steps may be performed during the simulation (on-the-fly mode) or as a post-process of the output files (offline mode). The predictions of the module have been compared with experimental data in terms of energy spectra, angular resolution, efficiency and back-projection image reconstruction. Consistent results within a 3-sigma interval were obtained for the energy spectra except for low energies where small differences arise. The angular resolution measure for incident photons of 1275 keV was also in good agreement between both data sets with a value close to 13°. Moreover, with the aim of demonstrating the versatility of such a tool the performance of two different Compton camera designs was evaluated and compared.

Compton camera study for high efficiency SPECT and benchmark with Anger system.

Single photon emission computed tomography (SPECT) is at present one of the major techniques for non-invasive diagnostics in nuclear medicine. The clinical routine is mostly based on collimated cameras, originally proposed by Hal Anger. Due to the presence of mechanical collimation, detection efficiency and energy acceptance are limited and fixed by the system's geometrical features. In order to overcome these limitations, the application of Compton cameras for SPECT has been investigated for several years. In this study we compare a commercial SPECT-Anger device, the General Electric HealthCare Infinia system with a High Energy General Purpose (HEGP) collimator, and the Compton camera prototype under development by the French collaboration CLaRyS, through Monte Carlo simulations (GATE-GEANT4 Application for Tomographic Emission-version 7.1 and GEANT4 version 9.6, respectively). Given the possible introduction of new radio-emitters at higher energies intrinsically allowed by the Compton camera detection principle, the two detectors are exposed to point-like sources at increasing primary gamma energies, from actual isotopes already suggested for nuclear medicine applications. The Compton camera prototype is first characterized for SPECT application by studying the main parameters affecting its imaging performance: detector energy resolution and random coincidence rate. The two detector performances are then compared in terms of radial event distribution, detection efficiency and final image, obtained by gamma transmission analysis for the Anger system, and with an iterative List Mode-Maximum Likelihood Expectation Maximization (LM-MLEM) algorithm for the Compton reconstruction. The results show for the Compton camera a detection efficiency increased by a factor larger than an order of magnitude with respect to the Anger camera, associated with an enhanced spatial resolution for energies beyond 500 keV. We discuss the advantages of Compton camera application for SPECT if compared to present commercial Anger systems, with particular focus on dose delivered to the patient, examination time, and spatial uncertainties.

Monte Carlo simulation of prompt γ-ray emission in proton therapy using a specific track length estimator.

A Monte Carlo (MC) variance reduction technique is developed for prompt-γ emitters calculations in proton therapy. Prompt-γ emitted through nuclear fragmentation reactions and exiting the patient during proton therapy could play an important role to help monitoring the treatment. However, the estimation of the number and the energy of emitted prompt-γ per primary proton with MC simulations is a slow process. In order to estimate the local distribution of prompt-γ emission in a volume of interest for a given proton beam of the treatment plan, a MC variance reduction technique based on a specific track length estimator (TLE) has been developed. First an elemental database of prompt-γ emission spectra is established in the clinical energy range of incident protons for all elements in the composition of human tissues. This database of the prompt-γ spectra is built offline with high statistics. Regarding the implementation of the prompt-γ TLE MC tally, each proton deposits along its track the expectation of the prompt-γ spectra from the database according to the proton kinetic energy and the local material composition. A detailed statistical study shows that the relative efficiency mainly depends on the geometrical distribution of the track length. Benchmarking of the proposed prompt-γ TLE MC technique with respect to an analogous MC technique is carried out. A large relative efficiency gain is reported, ca. 10(5).

Monte Carlo comparison of x-ray and proton CT for range calculations of proton therapy beams.

Proton computed tomography (CT) has been described as a solution for imaging the proton stopping power of patient tissues, therefore reducing the uncertainty of the conversion of x-ray CT images to relative stopping power (RSP) maps and its associated margins. This study aimed to investigate this assertion under the assumption of ideal detection systems. We have developed a Monte Carlo framework to assess proton CT performances for the main steps of a proton therapy treatment planning, i.e. proton or x-ray CT imaging, conversion to RSP maps based on the calibration of a tissue phantom, and proton dose simulations. Irradiations of a computational phantom with pencil beams were simulated on various anatomical sites and the proton range was assessed on the reference, the proton CT-based and the x-ray CT-based material maps. Errors on the tissue's RSP reconstructed from proton CT were found to be significantly smaller and less dependent on the tissue distribution. The imaging dose was also found to be much more uniform and conformal to the primary beam. The mean absolute deviation for range calculations based on x-ray CT varies from 0.18 to 2.01 mm depending on the localization, while it is smaller than 0.1 mm for proton CT. Under the assumption of a perfect detection system, proton range predictions based on proton CT are therefore both more accurate and more uniform than those based on x-ray CT.

Technical Note: Experimental carbon ion range verification in inhomogeneous phantoms using prompt gammas.

PURPOSE: The purpose of this study was to experimentally assess the possibility to monitor carbon ion range variations--due to tumor shift and/or elongation or shrinking--using prompt-gamma (PG) emission with inhomogeneous phantoms. Such a study is related to the development of PG monitoring techniques to be used in a carbon ion therapy context. METHODS: A 95 MeV/u carbon ion beam was used to irradiate phantoms with a variable density along the ion path to mimic the presence of bone and lung in homogeneous humanlike tissue. PG profiles were obtained after a longitudinal scan of the phantoms. A setup comprising a narrow single-slit collimator and two detectors placed at 90° with respect to the beam axis was used. The time of flight technique was applied to allow the selection between PG and background events. RESULTS: Using the positions at 50% entrance and 50% falloff of the PG profiles, a quantity called prompt-gamma profile length (PGPL) is defined. It is possible to observe shifts in the PGPL when there are absolute ion range shifts as small as 1-2 mm. Quantitatively, for an ion range shift of -1.33 ± 0.46 mm (insertion of a Teflon slab), a PGPL difference of -1.93 ± 0.58 mm and -1.84 ± 1.27 mm is obtained using a BaF2 and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 ± 0.42 mm (insertion of a lung-equivalent material slab) is considered, the difference is of 4.10 ± 0.54 and 4.39 ± 0.80 mm for the same detectors. CONCLUSIONS: Herein, experimental evidence of the usefulness of employing PG to monitor carbon ion range using inhomogeneous phantoms is presented. Considering the homogeneous phantom as reference, the results show that the information provided by the PG emission allows for detecting ion range shifts as small as 1-2 mm. When considering the expected PG emission from an energy slice in a carbon ion therapy scenario, the experimental setup would allow to retrieve the same PGPL as the high statistics of the full experimental dataset in 58% of the times. However, this success rate increases to 93% when using a better optimized setup by means of Monte Carlo simulations.

Absolute prompt-gamma yield measurements for ion beam therapy monitoring.

Prompt-gamma emission detection is a promising technique for hadrontherapy monitoring purposes. In this regard, obtaining prompt-gamma yields that can be used to develop monitoring systems based on this principle is of utmost importance since any camera design must cope with the available signal. Herein, a comprehensive study of the data from ten single-slit experiments is presented, five consisting in the irradiation of either PMMA or water targets with lower and higher energy carbon ions, and another five experiments using PMMA targets and proton beams. Analysis techniques such as background subtraction methods, geometrical normalization, and systematic uncertainty estimation were applied to the data in order to obtain absolute prompt-gamma yields in units of prompt-gamma counts per incident ion, unit of field of view, and unit of solid angle. At the entrance of a PMMA target, where the contribution of secondary nuclear reactions is negligible, prompt-gamma counts per incident ion, per millimetre and per steradian equal to (124 ± 0.7stat ± 30sys) × 10(-6) for 95 MeV u(-1) carbon ions, (79 ± 2stat ± 23sys) × 10(-6) for 310 MeV u(-1) carbon ions, and (16 ± 0.07stat ± 1sys) × 10(-6) for 160 MeV protons were found for prompt gammas with energies higher than 1 MeV. This shows a factor 5 between the yields of two different ions species with the same range in water (160 MeV protons and 310 MeV u(-1) carbon ions). The target composition was also found to influence the prompt-gamma yield since, for 300/310 MeV u(-1) carbon ions, a 42% greater yield ((112 ± 1stat ± 22sys) × 10(-6) counts ion(-1) mm(-1) sr(-1)) was obtained with a water target compared to a PMMA one.

Design optimisation of a TOF-based collimated camera prototype for online hadrontherapy monitoring.

Hadrontherapy is an innovative radiation therapy modality for which one of the main key advantages is the target conformality allowed by the physical properties of ion species. However, in order to maximise the exploitation of its potentialities, online monitoring is required in order to assert the treatment quality, namely monitoring devices relying on the detection of secondary radiations. Herein is presented a method based on Monte Carlo simulations to optimise a multi-slit collimated camera employing time-of-flight selection of prompt-gamma rays to be used in a clinical scenario. In addition, an analytical tool is developed based on the Monte Carlo data to predict the expected precision for a given geometrical configuration. Such a method follows the clinical workflow requirements to simultaneously have a solution that is relatively accurate and fast. Two different camera designs are proposed, considering different endpoints based on the trade-off between camera detection efficiency and spatial resolution to be used in a proton therapy treatment with active dose delivery and assuming a homogeneous target.

Assessment and improvements of Geant4 hadronic models in the context of prompt-gamma hadrontherapy monitoring.

Monte Carlo simulations are nowadays essential tools for a wide range of research topics in the field of radiotherapy. They also play an important role in the effort to develop a real-time monitoring system for quality assurance in proton and carbon ion therapy, by means of prompt-gamma detection. The internal theoretical nuclear models of Monte Carlo simulation toolkits are of decisive importance for the accurate description of neutral or charged particle emission, produced by nuclear interactions between beam particles and target nuclei. We assess the performance of Geant4 nuclear models in the context of prompt-gamma emission, comparing them with experimental data from proton and carbon ion beams. As has been shown in the past and further indicated in our study, the prompt-gamma yields are consistently overestimated by Geant4 by a factor of about 100% to 200% over an energy range from 80 to 310 MeV/u for the case of (12)C, and to a lesser extent for 160 MeV protons. Furthermore, we focus on the quantum molecular dynamics (QMD) modeling of ion-ion collisions, in order to optimize its description of light nuclei, which are abundant in the human body and mainly anticipated in hadrontherapy applications. The optimization has been performed by benchmarking QMD free parameters with well established nuclear properties. In addition, we study the effect of this optimization on charged particle emission. With the usage of the proposed parameter values, discrepancies reduce to less than 70%, with the highest values being attributed to the nucleon-ion induced prompt-gammas. This conclusion, also confirmed by the disagreement we observe in the case of proton beams, indicates the need for further investigation on nuclear models which describe proton and neutron induced nuclear reactions.

Real-time proton beam range monitoring by means of prompt-gamma detection with a collimated camera.

Prompt-gamma profile was measured at WPE-Essen using 160 MeV protons impinging a movable PMMA target. A single collimated detector was used with time-of-flight (TOF) to reduce the background due to neutrons. The target entrance rise and the Bragg peak falloff retrieval precision was determined as a function of incident proton number by a fitting procedure using independent data sets. Assuming improved sensitivity of this camera design by using a greater number of detectors, retrieval precisions of 1 to 2 mm (rms) are expected for a clinical pencil beam. TOF improves the contrast-to-noise ratio and the performance of the method significantly.

Machine learning-based patient specific prompt-gamma dose monitoring in proton therapy.

Online dose monitoring in proton therapy is currently being investigated with prompt-gamma (PG) devices. PG emission was shown to be correlated with dose deposition. This relationship is mostly unknown under real conditions. We propose a machine learning approach based on simulations to create optimized treatment-specific classifiers that detect discrepancies between planned and delivered dose. Simulations were performed with the Monte-Carlo platform Gate/Geant4 for a spot-scanning proton therapy treatment and a PG camera prototype currently under investigation. The method first builds a learning set of perturbed situations corresponding to a range of patient translation. This set is then used to train a combined classifier using distal falloff and registered correlation measures. Classifier performances were evaluated using receiver operating characteristic curves and maximum associated specificity and sensitivity. A leave-one-out study showed that it is possible to detect discrepancies of 5 mm with specificity and sensitivity of 85% whereas using only distal falloff decreases the sensitivity down to 77% on the same data set. The proposed method could help to evaluate performance and to optimize the design of PG monitoring devices. It is generic: other learning sets of deviations, other measures and other types of classifiers could be studied to potentially reach better performance. At the moment, the main limitation lies in the computation time needed to perform the simulations.

Interaction vertex imaging (IVI) for carbon ion therapy monitoring: a feasibility study.

Proton imaging can be seen as a powerful technique for online monitoring of ion range during carbon ion therapy irradiations. Indeed, a large number of secondary protons are created during nuclear reactions, and many of these protons are likely to escape from the patient even for deep-seated tumors, carrying accurate information on the reaction vertex position. Two detection techniques have been considered: (i) double-proton detection by means of two forward-located trackers and (ii) single-proton detection in coincidence with the incoming carbon ion detected by means of a beam hodoscope. Geant4 simulations, validated by proton yield measurements performed at GANIL and GSI, show that ion-range monitoring is accessible on a pencil-beam basis with the single-proton imaging technique. Millimetric precision on the Bragg peak position is expected in the ideal case of homogeneous targets. The uncertainties in more realistic conditions should be investigated, in particular the influence of tissue heterogeneity in the very last part of the ion path (about 20 mm).

Real-time monitoring of the Bragg-peak position in ion therapy by means of single photon detection.

For real-time monitoring of the longitudinal position of the Bragg-peak during an ion therapy treatment, a novel non-invasive technique has been recently proposed that exploits the detection of prompt gamma-rays issued from nuclear fragmentation. Two series of experiments have been performed at the GANIL and GSI facilities with 95 and 305 MeV/u (12)C(6+) ion beams stopped in PMMA and water phantoms. In both experiments, a clear correlation was obtained between the carbon ion range and the prompt photon profile. Additionally, an extensive study has been performed to investigate whether a prompt neutron component may be correlated with the carbon ion range. No such correlation was found. The present paper demonstrates that a collimated set-up can be used to detect single photons by means of time-of-flight measurements, at those high energies typical for ion therapy. Moreover, the applicability of the technique both at cyclotron and at synchrotron facilities is shown. It is concluded that the detected photon count rates provide sufficiently high statistics to allow real-time control of the longitudinal position of the Bragg-peak under clinical conditions.

Fission time measurements: a new probe into superheavy element stability.

Reaction mechanism analyses performed with a 4pi detector for the systems 208Pb + Ge, 238U + Ni and 238U + Ge, combined with analyses of the associated reaction time distributions, provide us with evidence for nuclei with Z=120 and 124 living longer than 10(-18) s and arising from highly excited compound nuclei. By contrast, the neutron deficient nuclei with Z=114 possibly formed in 208Pb + Ge reactions have shorter lifetimes, close to or below the sensitivity limit of the experiment.

Measurement of vacuum-assisted photoionization at 1 GeV for Au and Ag targets.

We report a measurement of photon impact ionization of K and L shell of Au and K shell of Ag targets in the 1-GeV energy range. We show that the cross section is dominated by a contribution from a new channel called vacuum-assisted photoionization. In this process the energy-momentum balance associated with the removal of the innershell electron is obtained by conversion of a high-energy photon into an electron-positron pair. This measurement is consistent with the theoretical prediction that vacuum-assisted photoionization is the most probable ionization mechanism at very high energies.

Strong evidence for enhanced multiple electron capture from surfaces in 46 MeV/u Pb81+ collisions with thin carbon foils.

Strong evidence has been found for enhanced multiple electron capture into 46 MeV/u Pb81+ with a significant contribution from the entrance surface of thin carbon foils. Capture of up to five electrons has been observed. The multiple electron capture yield is found to increase with decreasing target thickness for thin targets. A simple model describing the data and showing the importance of capture from surfaces is discussed. Further evidence is found for a pronounced asymmetry between electron capture at the entrance and the exit surfaces. Absolute yields for multiple electron capture and projectile ionization are presented. The experimental total cross sections for single capture and ionization agree well with theory.