Bragg Peak Location Research Articles

Light-transport incorporated plastic scintillator response to prompt gamma-rays for use in range verification of proton therapy

In this study, the prompt gamma-rays (PGs) produced during the interactions of proton beams of various energies have been investigated using the MCNPX2.6 Monte Carlo code. Having considered a detection setup consisting of a thick lead collimator and a commercial plastic scintillator, the event-by-event data, generated by the PTRAC card of the MCNPX code, when the scintillator is exposed to PGs have been extracted before they are used in a dedicated light transport code, PHOTRACK. The plastic scintillator response when it is moved along the phantom axis determines the flux variation of proton-induced PGs which can be further related to the longitudinal deposition energy profile of protons, i.e., the Bragg curve. The present study shows that the Bragg peak location is ∼3.7 cm after the PG peak for different proton energies of interest. The uncertainty in the Bragg peak location data is about 0.02 cm which can be improved by taking into account the precise electron-transport simulation details.

Theoretical approaches and Monte Carlo simulations in a clinical proton beam

Proton therapy is an interesting alternative to conventional radiotherapy, especially for treating localized tumors near important and/or sensitive parts of the human body. Protons, due to their electric charge and mass, interact with the propagating media in such a way that a well localized maximum - known as the Bragg peak - is observed if a depth dose deposition curve is plotted. Since the Bragg peak location depends on the initial proton energy beam, by adjusting this parameter it can be placed over the tumor to be treated. In addition, because the dose deposition goes to zero right after this peak, the health tissue after the tumor is spared if proton therapy is adopted. However, despite the aforementioned advantages, many issues prevent a wider adoption of proton therapy over radiotherapy. In addition to the very high implementation cost, unsolved technical issues, such as, the uncertainty in the proton beam range within the medium, or the correct dose prediction at the Bragg peak, must be addressed. This research aims to investigate the validity of theoretical approximations for the solution of Bethe equation. Such approaches are compared to results from Monte Carlo simulations, executed with the MCNPX code, and reference values ​​from the literature as well for the proton beam range and the energy deposition in the medium. A parameter is proposed and adopted to quantify the global difference between the theoretical approximations evaluated in this work with respect to the Monte Carlo simulation results.

Experimental demonstration of accurate Bragg peak localization with ionoacoustic tandem phase detection (iTPD)

Accurate knowledge of the exact stopping location of ions inside the patient would allow full exploitation of their ballistic properties for patient treatment. The localized energy deposition of a pulsed particle beam induces a rapid temperature increase of the irradiated volume and leads to the emission of ionoacoustic (IA) waves. Detecting the time-of-flight (ToF) of the IA wave allows inferring information on the Bragg peak location and can henceforth be used for in-vivo range verification. A challenge for IA is the poor signal-to-noise ratio at clinically relevant doses and viable machines. We present a frequency-based measurement technique, labeled as ionoacoustic tandem phase detection (iTPD) utilizing lock-in amplifiers. The phase shift of the IA signal to a reference signal is measured to derive the ToF. Experimental IA measurements with a 3.5 MHz lead zirconate titanate (PZT) transducer and lock-in amplifiers were performed in water using 22 MeV proton bursts. A digital iTPD was performed in-silico at clinical dose levels on experimental data obtained from a clinical facility and secondly, on simulations emulating a heterogeneous geometry. For the experimental setup using 22 MeV protons, a localization accuracy and precision obtained through iTPD deviates from a time-based reference analysis by less than 15 μm. Several methodological aspects were investigated experimentally in systematic manner. Lastly, iTPD was evaluated in-silico for clinical beam energies indicating that iTPD is in reach of sub-mm accuracy for fractionated doses < 5 Gy. iTPD can be used to accurately measure the ToF of IA signals online via its phase shift in frequency domain. An application of iTPD to the clinical scenario using a single pulsed beam is feasible but requires further development to reach <1 Gy detection capabilities.

Analysis of Bragg curve parameters and lateral straggle for proton and carbon beams

Heavy ions have varying effects on the target. The most important factor in comparing this effect is Linear Energy Transfer (LET). Protons and carbons are heavy ions with high LET. Since these ions lose energy through collisions as they move through the tissue, their range is not long. This loss of energy increases along the way, and the maximum energy loss is reached at the end of the range. This whole process is represented by the Bragg curve. The input dose of the Bragg curve, full width at half maximum (FWHM) value, Bragg peak amplitude and position, and Penumbra thickness are important factors in determining which particle is advantageous in tumor treatment. While heavy ions move through the tissue, small deviations occur in their direction of travel due to Coulomb collisions. These small deviations cause lateral straggle in the dose profile. Lateral straggle is important in determining the type and energy of the particle used in tumor treatments close to critical organs. In our study, when the water phantom of protons and carbon beams with different energies is taken into consideration, the input dose, FWHM value, peak amplitude and position, penumbra thickness and lateral straggle are calculated using the TRIM code and the results are compared with Monte Carlo (MC) simulation. It was found that the proton has an average of 63% more FWHM and 53% more Penumbra than the carbon ion. The carbon ion has an average of 28-45 times greater Bragg peak amplitude at the same Bragg peak location than the proton. It was observed that the proton scattered approximately 70% more in lateral straggle. The difference was found to be around 1.32 mm. In line with all these results, the most commonly used proton and carbon heavy ions in hadron therapy applications were compared.

Evaluation of dose distribution from 12C ion in radiation therapy by FLUKA code

Heavy ions have a high potential for destroying deep tumors that carry the highest dose at the peak of Bragg. The peak caused by a single-energy carbon beam is too narrow, which requires special measures for improvement. Here, carbon-12 (12C) ion with different energies has been used as a source for calculating the dose distribution in the water phantom, soft tissue and bone by the code of Monte Carlo-based FLUKA code. By increasing the energy of the initial beam, the amount of absorbed dose at Bragg peak in all three targets decreased, but the trend for this reduction was less severe in bone. While the maximum absorbed dose per bone-mass unit in energy of 200 MeV/u was about 30% less than the maximum absorbed dose per unit mass of water or soft tissue, it was merely 2.4% less than soft tissue in 400 MeV/u. The simulation result showed a good agreement with experimental data at GSI Darmstadt facility of biophysics group by 0.15 cm average accuracy in Bragg peak positioning. From 200 to 400 MeV/u incident energy, the Bragg peak location increased about 18 cm in soft tissue. Correspondingly, the bone and soft tissue revealed a reduction dose ratio by 2.9 and 1.9. Induced neutrons did not contribute more than 1.8% to the total energy deposited in the water phantom. Also during 12C ion bombardment, secondary fragments showed 76% and 24% of primary 200 and 400 MeV/u, respectively, were present at the Bragg-peak position. The combined treatment of carbon ions with neutron or electron beams may be more effective in local dose delivery and also treating malignant tumors.

Thermoacoustic Range Verification in the Presence of Acoustic Heterogeneity and Soundspeed Errors– Accuracy and Robustness Relative to Live Ultrasound Images

Lack of online range verification limits efficacy of particle therapy for many tumor sites. Real-time thermoacoustic range verification could enable more aggressive treatment planning and hypofractionation for tumor sites that can be imaged with ultrasound during treatment. Our objective was to experimentally demonstrate accuracy and robustness of thermoacoustic range estimates relative to ultrasound images despite acoustic heterogeneity and discrepancies between assumed and true soundspeed. Prior results were for weak acoustic scatterers with known soundspeeds. 250 ns pulses of 0.26 Gy of 16 MeV protons and 2.3 Gy of 60 MeV helium ions were delivered to water and oil targets, respectively. Thermoacoustic signals with DC-4 MHz bandwidth were detected by a 96-channel ultrasound array placed 6-10 cm distal to the Bragg peak. One-way beamforming with an assumed soundspeed was performed to estimate range. The same soundspeed and transducer array were used to generate ultrasound images via two-way ultrasound beamforming. An air gap phantom displaced the Bragg peak by 6.5 mm to demonstrate accuracy. The scanner’s soundspeed setting was altered by ±5% to demonstrate robustness to soundspeed errors. Tissue mimicking gelatin and a 5 mm thick bone sample were introduced to demonstrate robustness to acoustic heterogeneity. Single ion pulse measurements sufficed during the helium run, but signal averaging was required for protons. Estimates of the entry point agreed with the air-target interface in ultrasound images and range estimates agreed with Monte Carlo simulations to within 300 μm microns, even when TA emissions traveled through a strong acoustic scatterer. Estimated Bragg peak locations were translated 6.5 mm by the air gap phantom and correctly identified scenarios when the beam stopped inside bone, but did not accurately estimate range in bone. Soundspeed errors dilate and acoustic heterogeneities deform ultrasound images. Thermoacoustic range estimates are transformed similarly and are robust relative to ultrasound images of underlying anatomy. When the target can be visualized with ultrasound during treatment, thermoacoustic range verification may enable real-time motion management and range verification. Therapeutic systems deliver higher (200+ MeV) energy protons using pulse durations exceeding 5 μs and generate thermoacoustic emissions with sonar bandwidths (DC-100 kHz). Therefore, custom acoustic hardware will be required to detect low frequency thermoacoustic emissions and also generate high-resolution ultrasound images.Abstract 3713; Table 1Experimentwaterwater & bonewater & air gapsafflower oilIonprotonprotonproton4HeBeam Energy (MeV)16.0±0.1516.0±0.1516.0±0.1560.7±0.4Bragg curve FWHM (μm)390240390230distal HWTM (μm)1609016080Monte Carlo Range (mm)2.471.948.952.51Thermoacoustic Range (mm)2.65±0.091.36±0.616.59±0.042.76±0.04N8887 Open table in a new tab

Technical Note: Quality assurance of proton central axis pencil‐beam spread‐out Bragg peak using large‐diameter multilayer ionization chambers

The aim of this work is to describe a method of machine quality assurance (QA) by measuring proton spread-out Bragg peak constructed by the integrated depth dose via a large-diameter (12-cm) multilayer ionization chamber (LD-MLIC). Two types of contours are used to create the nominal plan. The final nominal plan is composed of mixed-energy proton pencil-beam spots located close to the central axis. The integrated depth dose (IDD) curve contains a flat SOBP region. The LD-MLIC-measured IDD was compared to the IDD curve exported from the treatment planning system (TPS). In addition, three plans with intentionally modified energy layers to simulate wrong-delivered energy layers were created and measured by the LD-MLIC. The water equivalent thickness (WET) difference between the inserted and replaced energies was 0.2cm. Six weeks of measurements were analyzed. A low-pass filter was introduced to mitigate the high-frequency noise in the IDD signal ratios. The filtered IDD signal ratios between the modified plans in different weeks and the baseline were used to check the energy accuracy. The differences between the LD-MLIC-measured and TPS-exported IDDs of the nominal plan were within 2% in most parts of the curve. Bumps/dips (~1%) were noted in the filtered IDD ratio between the modified plans and the baseline. The LD-MLIC can be used to check the accuracy of multiple energies Bragg peak locations quickly in proton machine QA. The LD-MLIC was sensitive in identifying an erroneous energy with 0.2cm in WET.

Thermoacoustic range verification in the presence of acoustic heterogeneity and soundspeed errors - Robustness relative to ultrasound image of underlying anatomy.

To demonstrate robustness of thermooacoustic range verification to acoustic heterogeneity and discrepancies between assumed and true propagation speed, i.e., soundspeed errors. A beam sweeper was used to deliver 250ns pulses that deposited 0.26Gy of 16MeV protons and 2.3Gy of 60MeV helium ions into water and oil targets, respectively. Thermoacoustic signals were detected by a 96-channel ultrasound array with a 1-4MHz sensitivity band (-6dB), bandpass filtered and backprojected to create thermoacoustic images in the plane of the ultrasound array. The same soundspeed and transducer array were used to estimate range and generate the ultrasound images onto which Bragg peak locations were overlaid. An air-gap phantom that displaced the Bragg peak by 6.5mm demonstrated accuracy. Robustness to soundspeed errors was demonstrated in a waterbath as the assumed propagation speed scanner setting was altered by . Tissue-mimicking gelatin and a bone sample were introduced to demonstrate robustness to acoustic heterogeneity relative to ultrasound images of the underlying morphology. Single ion pulse measurements sufficed during the helium run, but signal averaging was required for protons. Range and entry point into the target were estimated from data collected by transducers placed at least 6cm distal to the Bragg peak. When ultrasound images depicted the air-target interface where the beam enters, estimates of the entry point agreed with ultrasound images and range estimates agreed with Monte Carlo simulations to within 300μm, even when thermoacoustic emissions traveled through a strongly scattering bone sample. Estimated Bragg peak locations were translated 6.5mm by the air-gap phantom and correctly identified scenarios when the beam stopped inside the bone. Soundspeed errors dilate and acoustic heterogeneities deform ultrasound images. When thermoacoustic receivers are co-located with the ultrasound imaging array, the same transformations shift thermoacoustic range estimates. Therefore, thermoacoustic range verification is robust relative to ultrasound images of underlying anatomy. When the treatment target is visible in ultrasound, e.g., prostate, online thermoacoustic range estimates could verify that the treatment spot is inside the target.

Design of detector to monitor the Bragg peak location of carbon ions by means of prompt γ-ray measurements with Geant4

Real-time monitoring of the Bragg peak location of carbon ions is urgently required for the quality control of hadron therapy. In this study, we design an annular detector to monitor the Bragg peak location of carbon ions with Geant4 simulation . This $$360{^\circ }$$ surrounding structure has a high detection efficiency for the small-dose situation. The detector consists of a multilayered collimator system and an NaI scintillator for prompt gamma counting. The multilayered collimator includes a lead layer to prevent unwanted gammas and the paraffin and boron carbide layers to moderate and capture fast neutrons . An inclination of the detector further diminishes the background signal caused by neutrons. The detector, with optimized parameters, is applicable to carbon ions of different energies. In addition, the scintillator is replaced by an improved EJ301 organic liquid scintillator to discriminate gammas and neutrons. Inserting thin Fe slices into the liquid scintillator improves the energy deposition efficiency. The Bragg peak location of 200 MeV/u carbon ions can be monitored by prompt gamma detection with the improved liquid scintillator.

Two-stage ionoacoustic range verification leveraging Monte Carlo and acoustic simulations to stably account for tissue inhomogeneity and accelerator-specific time structure - A simulation study.

Range errors constrain treatment planning by limiting choice of ion beam angles and requiring large margins. Ionoacoustic range verification requires recovering the location of an acoustic source from low frequency signals. A priori information is applied to stably overcome resolution limits of inverse acoustic source imaging in this simulation study. In particular, the accuracy and robustness of ionoacoustic range verification for lateral and oblique delivery of high-energy protons to the prostate is examined. Dose maps were computed using GEANT4 Monte Carlo simulations via the TOPAS user interface. Thermoacoustic pulses were propagated using k-Wave software, with initial pressures corresponding to instantaneous dose deposition and piecewise constant maps of tissue properties derived from the planning CT. A database of dose maps with corresponding thermoacoustic emissions and Bragg peak locations, referred to as "control points," were precomputed. Corresponding thermoacoustic emissions were also precomputed. Pulses were recorded at four coplanar locations corresponding to the outer surface of a virtual transrectal array. To model experimental beam delivery, k-Wave results were convolved in time with a Gaussian envelope to account for noninstantaneous proton delivery by a synchrocyclotron. Thermoacoustic pulses were bandlimited below 150 kHz, and amplitudes were directly proportional to charge delivered. To test robustness of our method, white noise was added. Range was estimated in a two-step process. The first step obtained a preliminary range estimate by one-way beamforming. The second step was taken using data corresponding to the "control point" nearest to the preliminary range estimate. For each receiver, the time of flight difference, ∆t, between the measured and control thermoacoustic signals were accurately estimated by applying the Fourier shift theorem. Receiver-Bragg peak distance was then estimated by adding vs ∆t to the known distance of the control point, where vs is soundspeed. A linear system of equations based upon all receiver locations and distances was solved to recover the Bragg peak location. All simulations were performed relative to the planning CT. Because ultrasound (US) images were not available, results were overlaid onto the planning CT. Beamformed estimates from noise-free data tracked all beam locations within 1 cm. Final estimates for oblique and lateral beams were accurate to within 1.0 and 1.6 mm respectively. Average errors of final range estimates for oblique beams from data with SNR = 0 dB were no greater than 2.0 mm. Ionoacoustic range verification may improve current practice. Ionoacoustic range estimates can be inherently co-registered to ultrasound images of underlying anatomy. To ensure estimates are robust in clinical practice, dose maps based upon the planning CT should be overlaid onto ultrasound volumes acquired at time of treatment and acoustic simulations re-computed to provide a database of control points and corresponding thermoacoustic emissions. Computation times for beamformed estimates are already fast enough for online range verification, but are not accurate enough for a measurement aperture limited to the surface of a transrectal ultrasound probe. Accelerated acoustic simulations will be required to enable online two-stage correction, but offline calculation is already suitable for adaptive planning.

Initial testing of a pixelated silicon detector prototype in proton therapy.

As technology continues to develop, external beam radiation therapy is being employed, with increased conformity, to treat smaller targets. As this occurs, the dosimetry methods and tools employed to quantify these fields for treatment also have to evolve to provide increased spatial resolution. The team at the University of Wollongong has developed a pixelated silicon detector prototype known as the dose magnifying glass (DMG) for real‐time small‐field metrology. This device has been tested in photon fields and IMRT. The purpose of this work was to conduct the initial performance tests with proton radiation, using beam energies and modulations typically associated with proton radiosurgery. Depth dose and lateral beam profiles were measured and compared with those collected using a PTW parallel‐plate ionization chamber, a PTW proton‐specific dosimetry diode, EBT3 Gafchromic film, and Monte Carlo simulations. Measurements of the depth dose profile yielded good agreement when compared with Monte Carlo, diode and ionization chamber. Bragg peak location was measured accurately by the DMG by scanning along the depth dose profile, and the relative response of the DMG at the center of modulation was within 2.5% of that for the PTW dosimetry diode for all energy and modulation combinations tested. Real‐time beam profile measurements of a 5 mm 127 MeV proton beam also yielded FWHM and FW90 within ±1 channel (0.1 mm) of the Monte Carlo and EBT3 film data across all depths tested. The DMG tested here proved to be a useful device at measuring depth dose profiles in proton therapy with a stable response across the entire proton spread‐out Bragg peak. In addition, the linear array of small sensitive volumes allowed for accurate point and high spatial resolution one‐dimensional profile measurements of small radiation fields in real time to be completed with minimal impact from partial volume averaging.

Thermoacoustic range verification using a clinical ultrasound array provides perfectly co-registered overlay of the Bragg peak onto an ultrasound image

The potential of particle therapy due to focused dose deposition in the Bragg peak has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying the location of the Bragg peak onto a standard ultrasound image. Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the cyclotron inflector. The chopper limited the train of bunches so that 2 Gy were delivered in . The ion pulse generated thermoacoustic pulses that were detected by a cardiac ultrasound array, which also produced a grayscale ultrasound image. A filtered backprojection algorithm focused the received signal to the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Phantom experiments performed with the cavity both empty and filled with olive oil confirmed that displacement of the Bragg peak due to anatomical change could be detected. Thermoacoustic range measurements in the waterbath agreed with Monte Carlo simulation within 1.2 mm. In the phantom, thermoacoustic range estimates and first-order range estimates from CT images agreed to within 1.5 mm.

MO-FG-CAMPUS-JeP1-01: Prompt Gamma Imaging with a Multi-Knife-Edge Slit Collimator: Evaluation for Use in Proton Beam Range Verification

Purpose: To evaluate and characterize a multi-slit collimated imaging system for use in prompt gamma range verification of proton therapy. Methods: Acrylic (PMMA) targets were irradiated with a 50 MeV proton beam. With the collimator placed 13 cm from the beam axis, photons of energy from 2–7 MeV were measured. Image reconstruction provided 2-dimensional distribution of gamma rays. Estimated Bragg peak location was compared with 1-dimensional profiles of photon images. Shifts in Bragg peak were simulated by physically moving the targets in 1 mm increments. Results: The imaging system measured prompt gamma emissions resulting from a 50 MeV proton beam, at currents up to 2 nA, incident on a PMMA target. Overall system detection efficiency was approximately 2.6×10−5 gamma/proton. With delivery of 1×1011 protons, shifts of 1 mm in the target location were detected in 2D prompt gamma images and 1D profiles. With delivery of 1×108 protons, shifts of approximately 3 mm were detectable. Conclusion: This work has characterized the performance of a prototype multi-slit collimated imaging system. The system can produce 2D images of prompt gamma distributions and detect shifts in Bragg peak location down to 1 mm. These results encourage further development and optimization of the system for clinical proton beam applications. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number: DEN979 through the Nuclear Science and Security Consortium.

TU-FG-BRB-09: Thermoacoustic Range Verification with Perfect Co-Registered Overlay of Bragg Peak onto Ultrasound Image

Purpose: The potential of particle therapy has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying thermoacoustic localization of the Bragg peak onto an ultrasound image. Methods: Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the inflector of the 88″ cyclotron at Lawrence Berkeley National Lab. 2 Gy were delivered in 2 µs by a beam with peak current of 2 µA. Thermoacoustic emissions were detected by a cardiac array and Verasonics V1 ultrasound system, which also generated a grayscale ultrasound image. 1024 thermoacoustic pulses were averaged before filtering and one-way beamforming focused signal onto the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Experiments were performed with the cavity both empty and filled with olive oil. Results: In the waterbath overlays of the Bragg peak agreed with Monte Carlo simulations to within 800±170 µm. Agreement within 1.3 ± 0.2 mm was achieved in the gelatin phantom, although relative stopping powers were estimated only to first order from CT scans. Protoacoustic signals were detected after travel from the Bragg peak through 29 mm and 65 mm of phantom material when the cavity was empty and full of olive oil, respectively. Conclusion: Protoacoustic range verification is feasible with a commercial clinical ultrasound array, but at doses exceeding the clinical realm. Further optimization of both transducer array and injection line chopper is required to enable range verification within a 2 Gy dose limit, which would enable online adaptive treatment. This work was supported in part by a UWM Intramural Instrumentation Grant and by the Director, Office of Science, Office of Nuclear Physics, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. YMQ was supported by a UWM-OUR summer fellowship.

Graphene-Based D-Shaped Polymer FBG for Highly Sensitive Erythrocyte Detection

Graphene-based silica fiber-optic sensors, with high sensitivity, fast response, and low cost, have shown great promise for gas sensing applications. In this letter, by covering a monolayer of p-doped graphene on a D-shaped microstructured polymer fiber Bragg grating (FBG), we propose and demonstrate a novel biochemical probe sensor, the graphene-based D-shaped polymer FBG (GDPFBG). Due to the graphene-based surface evanescent field enhancement, this sensor shows high sensitivity to detect surrounding biochemical parameters. By monitoring the Bragg peak locations of the GDPFBG online, human erythrocyte (red blood cell) solutions with different cellular concentrations ranging from 0 to $10^{\mathrm {\mathbf {4}}}$ ppm were detected precisely, with the maximum resolution of sub-ppm. Such a sensor is structurally compact, is clinically acceptable, and provides good recoverability, offering a state-of-the-art polymer-fiber-based sensing platform for highly sensitive in situ and in vivo cell detection applications.

Characterization and Correction of Bragg Peak Location Uncertainties Resulting From Inherent Uncertainty in Proton Stopping Powers

Characterization and Correction of Bragg Peak Location Uncertainties Resulting From Inherent Uncertainty in Proton Stopping Powers

MO‐FG‐303‐05: A Feasibility Study of Using a Cherenkov Detector Material with the Prompt Gamma Range Verification Technique in Proton Therapy

Purpose:To simulate the feasibility of a Cherenkov glass material for the determination of the penetration depth of therapeutic proton beams in water.Methods:Proton pencil beams of various energies incident onto a water phantom with dimensions of 5 × 5 × 30 cm3 were used for simulation with the Geant4 toolkit. The model used standard electromagnetic packages, packages based on binary‐cascade nuclear model, several decay modules (G4Decay, G4DecayPhysics, and G4RadioactiveDecayPhysics), and optical photon components (G4OpticalPhysics). A Cherenkov glass material was modeled as the detector medium (7.2 g of In2O3 + 90 g cladding, density of 2.82 g/cm3, Zeff = 33.7, index of refraction n(600 nm) = 1.56, and energy threshold of production Eth = 156 keV ). The emitted secondary particles are analyzed characterizing their timing, energy, and angular distributions. A feasibility analysis was conducted for a simplistic detector system using this material to locate the position of the Bragg Peak.Results:The escaping neutrons have energies ranging from thermal to the incident proton energy and the escaping photons have energies &gt;10 MeV. Photon peaks between 4 and 6 MeV were attributed to originate from direct proton interactions with 12C (∼ 4.4 MeV) and 1⁶O (∼ 6 MeV), respectively. The escaping photons are emitted isotropically, while low (≤10 MeV) and high (&gt;10 MeV) neutrons are isotropic and forward‐directional, respectively. The emissions of photons are categorized into prompt (∼ns) and delayed (∼min) where the prompt photons include the 4.4 and 6 MeV. The Cherenkov material had on average &lt;2% of neutron interactions while LYSO and BGO scintillators had a minimum of ∼50%. Our simplistic detector system was capable of discerning Bragg Peak locations using a timing discrimination of ∼50 ns.Conclusion:We investigate the viability of using the Cherenkov material for MeV photon detection medium for the prompt gamma technique.

64: DNA damage, protein expression and migration of melanoma cells irradiated with proton beam

64: DNA damage, protein expression and migration of melanoma cells irradiated with proton beam

Comparison of cellular lethality in DNA repair-proficient or -deficient cell lines resulting from exposure to 70 MeV/n protons or 290 MeV/n carbon ions

Charged particle therapy utilizing protons or carbon ions has been rapidly intensifying over recent years. The present study was designed to jointly investigate these two charged particle treatment modalities with respect to modeled anatomical depth-dependent dose and linear energy transfer (LET) deliveries to cells with either normal or compromised DNA repair phenotypes. We compared cellular lethality in response to dose, LET and Bragg peak location for accelerated protons and carbon ions at 70 and 290 MeV/n, respectively. A novel experimental live cell irradiation OptiCell™ in vitro culture system using three different Chinese hamster ovary (CHO) cells as a mammalian model was conducted. A wild-type DNA repair-competent CHO cell line (CHO 10B2) was compared to two other CHO cell lines (51D1 and xrs5), each genetically deficient with respect to one of the two major DNA repair pathways (homologous recombination and non-homologous end joining pathways, respectively) following genotoxic insults. We found that wild-type and homologous recombination-deficient (Rad51D) cellular lethality was dependent on both the dose and LET of the carbon ions, whereas it was only dependent on dose for protons. The non-homologous end joining deficient cell line (Ku80 mutant) showed nearly identical dose-response profiles for both carbon ions and protons. Our results show that the increasingly used modality of carbon ions as charged particle therapy is advantageous to protons in a radiotherapeutic context, primarily for tumor cells proficient in non-homologous end joining DNA repair where cellular lethality is dependent not only on the dose as in the case of more common photon therapeutic modalities, but more importantly on the carbon ion LETs. Genetic characterization of patient tumors would be key to individualize and optimize the selection of radiation modality, clinical outcome and treatment cost.

MO-A-213AB-06: Validation of Nuclear Reaction Models to Simulate Proton Therapy Range Verification Using Prompt Gamma-Rays.

The impact of nuclear reaction model differences on simulation of prompt gamma-ray imaging for proton therapy range verification was assessed. Four nuclear reaction models were used to simulate gamma emission in proton beams, and were validated against experimental cross-sections. Proton-induced nuclear reactions on carbon, oxygen, nitrogen and calcium were investigated with the Monte Carlo toolkits GEANT4 9.5 and MCNPX 2.7, and the dedicated nuclear reaction codes TALYS 1.4 and EMPIRE 3.1. Absolute cross-sections of discrete prompt gamma lines and the total gamma production were obtained for the 1-200 MeV incident proton energy range. They were compared to 34 discrete line measurements reported in literature. Using these cross-sections, we analyzed the gamma production along the path of proton beams passing through various tissues. The differences in absolute discrete line cross-sections as predicted by the models ranged from almost zero to an order of magnitude, depending on the gamma line and incident proton energy. Overall, the dedicated nuclear reaction codes provided a better fit to most experimental excitation functions. For a 150 MeV proton beam stopping in soft tissue, these differences amount to a variation by a factor of 4 of the gamma emission around the Bragg peak location. The maximum of gamma production near the end of proton range differed by 7 mm, and the change of the 50% emission fall-off position was 4 mm. There is a clear need for improvement of nuclear reaction models to accurately simulate proton range verification using prompt gamma-rays. Current simulation codes show large uncertainties in both the total gamma yield and the correlation of gamma emission with the proton Bragg peak. GEANT4 and MCNPX in particular appear to have limited predictive power.