Prompt Gamma Imaging Research Articles

Simulation of proton range monitoring in an anthropomorphic phantom using multi-slat collimators and time-of-flight detection of prompt-gamma quanta

Prompt-gamma (PG) imaging has the potential for monitoring proton therapy in real time. Different approaches are investigated. We focus on developing multi-slat collimators to image PG quanta, aiming at optimizing collimator performance to detect deviations in treatment delivery. We investigated six different multi-slat configurations, which have either optimal (analytical) intrinsic spatial resolution at fixed efficiency, or otherwise; at different distances from the proton pencil-beam axis (15 cm–35 cm). We used Geant4 to simulate irradiations of the head (energy: 130 MeV) and pelvis (200 MeV) of an anthropomorphic phantom, with and without physiologic/morphologic or setup changes of clinical dosimetric relevance. The particles escaping the phantom were transported through each of these multi-slat configurations and the gamma counts profiles were recorded at the collimator exit. Median filtering was applied to the registered PG-profiles to mitigate the effects of septa shadowing and statistical fluctuations. Time-of-flight discrimination was used to enhance the signal-to-background ratio, which appeared crucial for 200 MeV irradiations. Visual detection of the artificially introduced changes was possible by comparing the PG to the depth-dose profiles. Moreover, 2 mm range shifts could be detected in the head irradiation case using a simple linear regression fit to the falloff of the PG-profile. The influence of changes in complex, patient-like dose distributions on the PG-profiles obtained with multi-slat collimation is first studied in this work, which further gives insight on collimator design optimization and highlights its potential and simplicity for detecting proton treatment deviations over a wide range of Bragg peak positions.

Optimization of the Signal-to-Background Ratio in Prompt Gamma Imaging Using Energy and Shifting Time-of-Flight Discrimination: Experiments With a Scanning Parallel-Slit Collimator

Much attention is currently being paid to imaging prompt gamma (PG) rays for in vivo proton range monitoring in proton therapy. PG imaging using a collimator is affected by neutron-related background. We study the effectiveness of background reduction experimentally, using a scanning parallel-slit PG collimator as a simplified model of a multislat PG camera. The analysis is focused on the falloff region of the PG intensity profile near the Bragg peak, which is the typical region of interest for proton range estimation. Background reduction was studied for different energy windows, with and without a shifting time-of-flight window that takes into account the proton velocity within the phantom. Practical methods are put forward that apply to cyclotron-based pencil beams. The parallel-slit collimator was placed in front of arrays of cerium-doped lutetium yttrium silicate-coupled digital silicon photomultipliers, used to measure energy and time spectra together with intensity profiles of prompt events emitted from a polymethylmethacrylate phantom irradiated with a 160-MeV proton pencil beam. The best signal-to-background ratio of ~1.6 was similar to that obtained previously with a knife-edge-slit collimator. However, the slope-over-noise ratio in the PG-profile falloff region, was ~1.2 higher for the present collimator, given its better resolution.

OA051] Toward a new treatment planning system accounting for in-vivo proton range verification in proton therapy

Purpose Proton therapy is widely used in state-of-the-art radiotherapy. However, precision of proton therapy could be affected by proton range uncertainties due to e.g. anatomy change, patient setting uncertainties. Prompt gamma (PG) imaging is investigated to monitor proton range in vivo by detecting PG emitted by nuclear de-excitation processes in the beam path. Despite ideal correlation between the penetration depth of PG signal and proton range in most cases, few literature studies reported that this correlation could deteriorate because of tissue heterogeneities. Hence, in this study, we investigate a new treatment planning approach accounting for PG imaging. Methods A research computational platform, combining Monte Carlo (MC, Geant4) pre-calculated pencil beams (subPB) with the Matlab-based TPS engine CERR (A computational Environment for Radiotherapy Research), was introduced for treatment planning. To optimize current treatment plans considering PG imaging, first, a MC treatment plan is created using a particle extension of CERR. Thereby, the PG emission and dose distribution for each subPB is obtained. Secondly, the PG fall-off position is evaluated and compared to the proton range (80% distal dose fall-off) for all subPBs. SubPBs with reliable PG-dose correlation are visualized in terms of beam-eye-view location and individual dose delivery. Few of these “good-correlation” subPBs are boosted in the new treatment plan via manual or automated selection to enable good detectability. Then, a re-optimized plan is created and recalculated on the same patient CT using Geant4 for evaluation. Results The new treatment planning approach was applied to 3 head & neck tumor patients. The dose distribution of the original and re-optimized treatment plan was found to be of comparable dosimetric quality. The positions and PG-dose correlations of highest-intensity subPBs in the original plan were random, while in the optimized plan the highest-intensity subPBs are with good PG-dose correlation and uniformly distributed across the entire field for a reliable and thorough monitoring. Conclusions A new treatment planning approach has been proposed, which could improve the treatment planning process in proton therapy by integrating the PG-based in vivo monitoring of the beam range for a safer and more controllable proton treatment. EU-MSCA GA n. 675265 (OMA).

A low-count reconstruction algorithm for Compton-based prompt gamma imaging

The Compton camera is an imaging device which has been proposed to detect prompt gammas (PGs) produced by proton–nuclear interactions within tissue during proton beam irradiation. Compton-based PG imaging has been developed to verify proton ranges because PG rays, particularly characteristic ones, have strong correlations with the distribution of the proton dose. However, accurate image reconstruction from characteristic PGs is challenging because the detector efficiency and resolution are generally low. Our previous study showed that point spread functions can be incorporated into the reconstruction process to improve image resolution. In this study, we proposed a low-count reconstruction algorithm to improve the image quality of a characteristic PG emission by pooling information from other characteristic PG emissions. PGs were simulated from a proton beam irradiated on a water phantom, and a two-stage Compton camera was used for PG detection. The results show that the image quality of the reconstructed characteristic PG emission is improved with our proposed method in contrast to the standard reconstruction method using events from only one characteristic PG emission. For the 4.44 MeV PG rays, both methods can be used to predict the positions of the peak and the distal falloff with a mean accuracy of 2 mm. Moreover, only the proposed method can improve the estimated positions of the peak and the distal falloff of 5.25 MeV PG rays, and a mean accuracy of 2 mm can be reached.

EP-1801: Prompt gamma imaging for the identification of proton range deviations due to anatomical change

EP-1801: Prompt gamma imaging for the identification of proton range deviations due to anatomical change

Speedup Potential for Reconstruction Techniques for Prompt Gamma Imaging During Proton Radiotherapy

Proton beam radiation treatment was first proposed by Robert Wilson in 1946. The advantage of proton beam radiation is that the lethal dose of radiation is delivered by a sharp increase toward the end of the beam range. This sharp increase, known as the Bragg peak, allows for the possibility of reducing the exposure of healthy tissue to radiation when comparing to x-ray radiation treatment. As the proton beam interacts with the molecules in the body, gamma rays are emitted. The origin of the gamma rays gives the location of the proton beam in the body, therefore, gamma ray imaging allows physicians to better take advantage of the benefits of proton beam radiation. These gamma rays are detected using a Compton Camera (CC) while the SOE algorithm is used to reconstruct images of these gamma rays as they are emitted from the patient. This imaging occurs while the radiation dose is delivered, which would allow the physician to make adjustments in real time in the treatment room, provided the image reconstruction is computed fast enough. This project focuses on speeding up the image reconstruction software with the use of parallel computing techniques involving MPI. Additionally, we demonstrate the use of the VTune performance analyzer to identify bottlenecks in a parallel code. KEYWORDS: Proton Beam Therapy; Image Reconstruction; SOE Algorithm; Parallel Computing; High Performance Computing; Medical Imaging; Prompt Gamma Imaging; Radiotherapy

CeBr3 scintillators for 4He prompt gamma spectroscopy: Results from a Monte Carlo optimization study

Range uncertainties limit the potential of charged particle therapy. In vivo and online range verification techniques could increase the confidence in the dose delivery distribution and lead to more conformal treatments. Prompt gamma imaging and prompt gamma spectroscopy (PGS) have been demonstrated for such a purpose. The successful application of these techniques requires the development of a dedicated detector system optimized to the radiation energy ranges and the intensity. In this work, we investigated a detector system based on CeBr3 crystals capable of performing spectroscopy of the prompt gamma radiation induced by 4 He beams. We performed Monte Carlo simulations to optimize the detector system. The study was carried out both with the Geant4 toolkit and the FLUKA package. The simulated system consisted of a primary crystal for spectroscopy and secondary crystals for noise reduction in anticoincidence (AC). For comparison purposes, we considered a configuration without AC crystals. We first defined the dimensions of the primary cerium bromide (CeBr3 ) crystal and the secondary bismuth germanate (BGO) or CeBr3 crystals. We then evaluated their detection performance for monoenergetic gamma radiation up to 7MeV in such way that the probability of the photo-peak detection was maximized in comparison to the number of escape peak and Compton events. We simulated realistic prompt gamma radiation spectra induced by 4 He beams on homogeneous targets (water, graphite, and aluminum) and on implants (water with an aluminum insert). Finally, we tested the performances of the optimized systems in the detection of the realistic gamma spectra. The quantitative analysis was accomplished by comparing the signal-to-noise ratio between the different configurations and the ability to resolve the discrete reactions. We present the optimized dimensions for the primary CeBr3 crystals with and without AC shielding. The specific values are given over a wide range of crystal volumes. The results show an optimal primary CeBr3 crystal with an approximately diameter to length ratio of 1 without AC shielding and 0.5 with AC shielding. The secondary BGO and CeBr3 should have a transverse dimension of 3 and 4.56cm, respectively. The analysis of the prompt gamma spectra from 4 He beams highlighted the presence of specific discrete reactions not observed in 1 H studies, for example, 12 C transition 0+ (7.65MeV) →2+ (4.44MeV). This reaction is responsible for the generation of the 3.21MeV prompt gamma peak. The optimized primary crystal provides a significant increase in the signal-to-noise ratio together with an improved resolution of the discrete gamma lines, especially in the high-energy region. The detection configuration with an optimized anticoincidence crystal improved the signal-to-noise ratio up to a factor of 3.5. This work provides the optimal geometry for primary and secondary crystals to be used in range verification through PGS. The simulations show that such a PGS system may allow for the simultaneous detection of the discrete lines from a thin metal implant within a water phantom.

PSF reconstruction for Compton-based prompt gamma imaging

Compton-based prompt gamma (PG) imaging has been proposed for in vivo range verification in proton therapy. However, several factors degrade the image quality of PG images, some of which are due to inherent properties of a Compton camera such as spatial resolution and energy resolution. Moreover, Compton-based PG imaging has a spatially variant resolution loss. In this study, we investigate the performance of the list-mode ordered subset expectation maximization algorithm with a shift-variant point spread function (LM-OSEM-SV-PSF) model. We also evaluate how well the PG images reconstructed using an SV-PSF model reproduce the distal falloff of the proton beam. The SV-PSF parameters were estimated from simulation data of point sources at various positions. Simulated PGs were produced in a water phantom irradiated with a proton beam. Compared to the LM-OSEM algorithm, the LM-OSEM-SV-PSF algorithm improved the quality of the reconstructed PG images and the estimation of PG falloff positions. In addition, the 4.44 and 5.25 MeV PG emissions can be accurately reconstructed using the LM-OSEM-SV-PSF algorithm. However, for the 2.31 and 6.13 MeV PG emissions, the LM-OSEM-SV-PSF reconstruction provides limited improvement. We also found that the LM-OSEM algorithm followed by a shift-variant Richardson–Lucy deconvolution could reconstruct images with quality visually similar to the LM-OSEM-SV-PSF-reconstructed images, while requiring shorter computation time.

Progress towards a semiconductor Compton camera for prompt gamma imaging during proton beam therapy for range and dose verification

The main objective of this work is to test a new semiconductor Compton camera for prompt gamma imaging. Our device is composed of three active layers: a Si(Li) detector as a scatterer and two high purity Germanium detectors as absorbers of high-energy gamma rays. We performed Monte Carlo simulations using the Geant4 toolkit to characterise the expected gamma field during proton beam therapy and have made experimental measurements of the gamma spectrum with a 60 MeV passive scattering beam irradiating a phantom. In this proceeding, we describe the status of the Compton camera and present the first preliminary measurements with radioactive sources and their corresponding reconstructed images.

Pixelated prompt gamma imaging detector for online measurement of proton beam: Monte Carlo feasibility study by FLUKA

Increased accuracy of proton beam delivery provides additional benefits to the patients undergo the treatment. A prompt gamma imaging detector can provide additional information during the treatment, as the prompt gammas produced by the interactions between protons and human tissues are related to the range and profile of the beam in the patient. This paper makes a Monte Carlo feasibility study for a pixelated prompt gamma imaging detector which can not only measure the proton range but also merge the beam profile and 3D beam image inside the patient. FLUKA simulation result shows that this detector can reduce background noise and measure the range and beam profile by using of grated shielding material, vertical gammas selection and a 5 MeV energy window.

Sensitivity of a prompt-gamma slit-camera to detect range shifts for proton treatment verification

Background and purposeA prompt-gamma imaging (PGI) slit-camera was recently applied successfully in clinical proton treatments using pencil beam scanning (PBS) and double scattering (DS). However, its full capability under clinical conditions has still to be systematically evaluated. Here, the performance of the slit-camera is systematically assessed in well-defined error scenarios using realistic treatment deliveries to an anthropomorphic head phantom. Materials and methodsThe sensitivity and accuracy to detect introduced global and local range shifts with the slit-camera was investigated in PBS and DS irradiations. For PBS, measured PGI information of shifted geometries were compared spot-wise with un-shifted PGI information derived from either a reference measurement or a treatment-plan-based simulation. Furthermore, for DS and PBS the integral PGI signal of the whole field was evaluated. ResultsDeviations from the treatment plan were detected with an accuracy better than 2 mm in PBS. The PGI simulation accuracy was well below 1 mm. Interfractional comparisons are more affected by measurement noise. The field-integral PGI sum signal allows the detection of global shifts in DS. ConclusionsDetection of global and local range shifts under close-to-clinical conditions is possible with the PGI slit-camera. Especially for PBS, high sensitivity and high accuracy in shift detection were found.

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 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> 1-MeV equivalent neutrons/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> 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 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> 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 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> protons).

Characterization of high density SiPM non-linearity and energy resolution for prompt gamma imaging applications

Fondazione Bruno Kessler (FBK) (Trento, Italy) has recently introduced High Density (HD) and Ultra High-Density (UHD) SiPMs, featuring very small micro-cell pitch. The high cell density is a very important factor to improve the linearity of the SiPM in high-dynamic-range applications, such as the scintillation light readout in high-energy gamma-ray spectroscopy and in prompt gamma imaging for proton therapy. The energy resolution at high energies is a trade-off between the excess noise factor caused by the non-linearity of the SiPM and the photon detection efficiency of the detector. To study these effects, we developed a new setup that simulates the LYSO light emission in response to gamma photons up to 30 MeV, using a pulsed light source. We measured the non-linearity and energy resolution vs. energy of the FBK RGB-HD e RGB-UHD SiPM technologies. We considered five different cell sizes, ranging from 10 μm up to 25 μm. With the UHD technology we were able to observe a remarkable reduction of the SiPM non-linearity, less than 5% at 5 MeV with 10 μm cells, which should be compared to a non-linearity of 50% with 25 μm-cell HD-SiPMs. With the same setup, we also measured the different components of the energy resolution (intrinsic, statistical, detector and electronic noise) vs. cell size, over-voltage and energy and we separated the different sources of excess noise factor.

Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy

To report the first clinical results and value assessment of prompt gamma imaging for invivo proton range verification in pencil beam scanning mode. A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. In 6 treatment fractions recorded over 3weeks, the mean (± standard deviation)range shifts aggregated over all spots in 9 energy layers were -0.8±1.3mm for the lateral field, 1.7±0.7mm for the right-superior-oblique field, and -0.4±0.9mm for the vertex field. This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for invivo proton range verification and quantification of range uncertainties.

Development of a Compton camera for prompt-gamma medical imaging

A Compton camera-based detector system for photon detection from nuclear reactions induced by proton (or heavier ion) beams is under development at LMU Munich, targeting the online range verification of the particle beam in hadron therapy via prompt-gamma imaging. The detector is designed to be capable to reconstruct the photon source origin not only from the Compton scattering kinematics of the primary photon, but also to allow for tracking of the secondary Compton-scattered electrons, thus enabling a γ-source reconstruction also from incompletely absorbed photon events. The Compton camera consists of a monolithic LaBr3:Ce scintillation crystal, read out by a multi-anode PMT acting as absorber, preceded by a stacked array of 6 double-sided silicon strip detectors as scatterers. The detector components have been characterized both under offline and online conditions. The LaBr3:Ce crystal exhibits an excellent time and energy resolution. Using intense collimated 137Cs and 60Co sources, the monolithic scintillator was scanned on a fine 2D grid to generate a reference library of light amplitude distributions that allows for reconstructing the photon interaction position using a k-Nearest Neighbour (k-NN) algorithm. Systematic studies were performed to investigate the performance of the reconstruction algorithm, revealing an improvement of the spatial resolution with increasing photon energy to an optimum value of 3.7(1)mm at 1.33MeV, achieved with the Categorical Average Pattern (CAP) modification of the k-NN algorithm.

Experimental Verification of Key Cross Sections for Prompt-gamma Imaging in Proton Therapy

Experimental Verification of Key Cross Sections for Prompt-gamma Imaging in Proton Therapy

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ).For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2–5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained.With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

From prompt gamma distribution to dose: a novel approach combining an evolutionary algorithm and filtering based on Gaussian-powerlaw convolutions

Range verification and dose monitoring in proton therapy is considered as highly desirable. Different methods have been developed worldwide, like particle therapy positron emission tomography (PT-PET) and prompt gamma imaging (PGI). In general, these methods allow for a verification of the proton range. However, quantification of the dose from these measurements remains challenging. For the first time, we present an approach for estimating the dose from prompt γ-ray emission profiles. It combines a filtering procedure based on Gaussian-powerlaw convolution with an evolutionary algorithm. By means of convolving depth dose profiles with an appropriate filter kernel, prompt γ-ray depth profiles are obtained. In order to reverse this step, the evolutionary algorithm is applied. The feasibility of this approach is demonstrated for a spread-out Bragg-peak in a water target.

Estimating patient specific uncertainty parameters for adaptive treatment re-planning in proton therapy using in vivo range measurements and Bayesian inference: application to setup and stopping power errors

In proton therapy, quantification of the proton range uncertainty is important to achieve dose distribution compliance. The promising accuracy of prompt gamma imaging (PGI) suggests the development of a mathematical framework using the range measurements to convert population based estimates of uncertainties into patient specific estimates with the purpose of plan adaptation. We present here such framework using Bayesian inference. The sources of uncertainty were modeled by three parameters: setup bias m, random setup precision r and water equivalent path length bias u. The evolution of the expectation values E(m), E(r) and E(u) during the treatment was simulated. The expectation values converged towards the true simulation parameters after 5 and 10 fractions, for E(m) and E(u), respectively. E(r) settle on a constant value slightly lower than the true value after 10 fractions. In conclusion, the simulation showed that there is enough information in the frequency distribution of the range errors measured by PGI to estimate the expectation values and the confidence interval of the model parameters by Bayesian inference. The updated model parameters were used to compute patient specific lateral and local distal margins for adaptive re-planning.

Photon radiotherapy has reached its limit in terms of catching up dosimetrically with proton therapy.

Photon radiotherapy has reached its limit in terms of catching up dosimetrically with proton therapy.