LET dependence of the response of a PTW-60019 microDiamond detector in a 62 MeV proton beam

This study was initiated following conclusions from earlier experimental work, performed in a low-energy carbon ion beam, indicating a significant LET dependence of the response of a PTW-60019 microDiamond detector. The purpose of this paper is to present a comparison between the response of the same PTW-60019 microDiamond detector and an IBA Roos-type ionization chamber as a function of depth in a 62 MeV proton beam. Even though proton beams are considered as low linear energy transfer (LET) beams, the LET value increases slightly in the Bragg peak region. Contrary to the observations made in the carbon ion beam, in the 62 MeV proton beam good agreement is found between both detectors in both the plateau and the distal edge region. No significant LET dependent response of the PTW-60019 microDiamond detector is observed consistent with other findings for proton beams in the literature, despite this particular detector exhibiting a substantial LET dependence in a carbon ion beam.     

The determination of a dose deposited in reference medium due to (p,n) reaction occurring during proton therapy

AimThe aim of the investigation was to determine the undesirable dose coming from neutrons produced in reactions (p,n) in irradiated tissues represented by water.BackgroundProduction of neutrons in the system of beam collimators and in irradiated tissues is the undesirable phenomenon related to the application of protons in radiotherapy. It makes that proton beams are contaminated by neutrons and patients receive the undesirable neutron dose.Materials and methodsThe investigation was based on the Monte Carlo simulations (GEANT4 code). The calculations were performed for five energies of protons: 50 MeV, 55 MeV, 60 MeV, 65 MeV and 75 MeV. The neutron doses were calculated on the basis of the neutron fluence and neutron energy spectra derived from simulations and by means of the neutron fluence–dose conversion coefficients taken from the ICRP dosimetry protocol no. 74 for the antero-posterior irradiation geometry.ResultsThe obtained neutron doses are much less than the proton ones. They do not exceed 0.1%, 0.4%, 0.5%, 0.6% and 0.7% of the total dose at a given depth for the primary protons with energy of 50 MeV, 55 MeV, 60 MeV, 65 MeV and 70 MeV, respectively.ConclusionsThe neutron production takes place mainly along the central axis of the beam. The maximum neutron dose appears at about a half of the depth of the maximum proton dose (Bragg peak), i.e. in the volume of a healthy tissue. The doses of neutrons produced in the irradiated medium (water) are about two orders of magnitude less than the proton doses for the considered range of energy of protons.     

Measurement of stray neutron doses inside the treatment room from a proton pencil beam scanning system

PurposeTo measure the environmental doses from stray neutrons in the vicinity of a solid slab phantom as a function of beam energy, field size and modulation width, using the proton pencil beam scanning (PBS) technique.MethodMeasurements were carried out using two extended range WENDI-II rem-counters and three tissue equivalent proportional counters. Detectors were suitably placed at different distances around the RW3 slab phantom. Beam irradiation parameters were varied to cover the clinical ranges of proton beam energies (100–220 MeV), field sizes ((2 × 2)–(20 × 20) cm²) and modulation widths (0–15 cm).ResultsFor pristine proton peak irradiations, large variations of neutron H¹(10)/D were observed with changes in beam energy and field size, while these were less dependent on modulation widths. H¹(10)/D for pristine proton pencil beams varied between 0.04 μSv Gy⁻¹ at beam energy 100 MeV and a (2 × 2) cm² field at 2.25 m distance and 90° angle with respect to the beam axis, and 72.3 μSv Gy⁻¹ at beam energy 200 MeV and a (20 × 20) cm² field at 1 m distance along the beam axis.ConclusionsThe obtained results will be useful in benchmarking Monte Carlo calculations of proton radiotherapy in PBS mode and in estimating the exposure to stray radiation of the patient. Such estimates may be facilitated by the obtained best-fitted simple analytical formulae relating the stray neutron doses at points of interest with beam irradiation parameters.     

Optimization of an ultra-fast silicon detector for proton and carbon beams using GEANT4 Monte Carlo toolkit

AimThe purpose of this study was to investigate the crosstalk effects between adjacent pixels in a thin silicon detector with 50 um thickness.BackgroundThere are some limitations in the applications of detectors in hadron therapy. So it is necessary to have a detector with concurrent excellent time and resolution. In this work, the GEANT4 toolkit was applied to estimate the best value for energy cutoff in the thin silicon detector in order to optimize the detector.Materials and MethodsGEANT4 toolkit was applied to simulate the transport and interactions of particles. Calculations were performed for a thin silicon detector (2 cm × 2 cm×0.005 cm) irradiated by proton and carbon ion beams. A two-dimensional array of silicon pixels in the x-y plane with 100 um × 100 um × 50 um dimensions build the whole detector. In the end, the ROOT package is used to interpret and analyze the resultsResultsIt is seen that by the presence of energy cutoff, pixels with small deposited energy are ignored. The best values for energy cutoff are 0.01 MeV and 0.7 MeV for proton and carbon ion beams, respectively. By applying these energy cutoff values, efficiency and purity values are maximized and also minimum output errors are achieved.ConclusionsThe results are reasonable, good and useful to optimize the geometry of future silicon detectors in order to be used as beam monitoring in hadron therapy applications.     

Quality assurance of carbon ion and proton beams: A feasibility study for using the 2D MatriXX detector

PurposeThe quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements.MethodsMatriXX is a commercial detector composed of 32 × 32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44 MeV proton and a 221.45 MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia – Italy, and the results were analyzed and compared.ResultsThe sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230 μm for carbon ions and less than 100 μm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement.ConclusionsThe results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.     

Characterization of prompt gamma-ray emission with respect to the Bragg peak for proton beam range verification: A Monte Carlo study

In this paper we report a Geant4 simulation study to investigate the characteristic prompt gamma (PG) emission in a water phantom for real-time monitoring of the Bragg peak (BP) during proton beam irradiation. The PG production, emission spatial correlation with the BP, and position preference for detection with respect to the BP have been quantified in different PG energy windows as a function of proton pencil-beam energy from 100 to 200 MeV. The PG response to small BP shifts was evaluated using a 2 cm-thick slab with different human body materials embedded in a water phantom. Our results show that the prominent characteristic PG emissions of 4.44, 5.21 and 6.13 MeV exhibit distinctive correlation with the dose deposition curve. The accuracy in BP position identification using these characteristic PG rays is highly consistent as the beam energy increases from 100 to 200 MeV. There exists a position preference for PG detection with respect to the BP position, which has a strong dependence on the proton beam energy and PG energies. It was also observed that a submillimeter shift of the BP position can be realized by using PG signals. These results indicate that the characteristic PG signal is sensitive and reliable for BP tracking. Although the maximization of the PG measurement associated with the BP is difficult, it can be optimized with energy and detection position preferences.     

A neutron activation technique for manganese measurements in humans

Manganese (Mn) is an essential element for humans, animals, and plants and is required for growth, development, and maintenance of health. Studies show that Mn metabolism is similar to that of iron, therefore, increased Mn levels in humans could interfere with the absorption of dietary iron leading to anemia. Also, excess exposure to Mn dust, leads to nervous system disorders similar to Parkinson's disease. Higher exposure to Mn is essentially related to industrial pollution. Thus, there is a benefit in developing a clean non-invasive technique for monitoring such increased levels of Mn in order to understand the risk of disease and development of appropriate treatments.To this end, the feasibility of Mn measurements with their minimum detection limits (MDL) has been reported earlier from the McMaster group. This work presents improvement to Mn assessment using an upgraded system and optimized times of irradiation and counting for induced gamma activity of Mn. The technique utilizes the high proton current Tandetron accelerator producing neutrons via the ⁷Li(p,n)⁷Be reaction at McMaster University and an array of nine NaI (Tl) detectors in a 4π geometry for delayed counting of gamma rays. The neutron irradiation of a set of phantoms was performed with protocols having different proton energy, current and time of irradiation. The improved MDLs estimated using the upgraded set up and constrained timings are reported as 0.67 μgMn/gCa for 2.3 MeV protons and 0.71 μgMn/gCa for 2.0 MeV protons. These are a factor of about 2.3 times better than previous measurements done at McMaster University using the in vivo set-up. Also, because of lower dose-equivalent and a relatively close MDL, the combination of: 2.0 MeV; 300 μA; 3 min protocol is recommended as compared to 2.3 MeV; 400 μA; 45 s protocol for further measurements of Mn in vivo.     

Highly resolved proton matrix ENDOR of oriented photosystem II membranes in the S2 state

Proton matrix ENDOR was performed to investigate the protons close to the manganese cluster in oriented samples of photosystem II (PS II). Eight pairs of ENDOR signals were detected in oriented PS II membranes. At an angle of θ = 0° between the membrane normal vector n and the external field H₀, five pairs of ENDOR signals were exchangeable in D₂O medium and three pairs were not exchangeable in D₂O medium. The hyperfine splitting of 3.60 MHz at θ = 0° increased to 3.80 MHz at θ = 90°. The non-exchangeable signals with 1.73 MHz hyperfine splitting at θ = 0°, which were assigned to a proton in an amino acid residue, were not detected at θ = 90° in oriented PS II or in non-oriented PS II. Highly resolved spectra show that only limited numbers of protons were detected by CW-ENDOR spectra, although many protons were located near the CaMn₄O₅ cluster. The detected exchangeable protons were proposed to arise from the protons belonging to the water molecules, labeled W1-W4 in the 1.9 Å crystal structure, directly ligated to the CaMn₄O₅ cluster, and nearby amino-acid residue.     

Local dose enhancement of proton therapy by ceramic oxide nanoparticles investigated with Geant4 simulations

Nanoparticles (NPs) have been shown to enhance X-ray radiotherapy and proton therapy of cancer. The effectiveness of radiation damage is enhanced in the presence of high atomic number (high-Z) NPs due to increased production of low energy, higher linear energy transfer (LET) secondary electrons when NPs are selectively internalized by tumour cells. This work quantifies the local dose enhancement produced by the high-Z ceramic oxide NPs Ta₂O₅ and CeO₂, in the target tumour, for the first time in proton therapy, by means of Geant4 simulations. The dose enhancement produced by the ceramic oxides is compared against gold NPs. The energy deposition on a nanoscale around a single nanoparticle of 100 nm diameter is investigated using the Geant4-DNA extension to model particle interactions in the water medium. Enhancement of energy deposition in nano-sized shells of water, local to the NP boundary, ranging between 14% and 27% was observed for proton energies of 5 MeV and 50 MeV, depending on the NP material. Enhancement of electron production and energy deposition can be correlated to the direct DNA damage mechanism if the NP is in close proximity to the nucleus.     

Neutron shielding for a new projected proton therapy facility: A Geant4 simulation study

In this work, we used the Monte Carlo-based Geant4 simulation toolkit to calculate the ambient dose equivalents due to the secondary neutron field produced in a new projected proton therapy facility. In particular the facility geometry was modeled in Geant4 based on the CAD design. Proton beams were originated with an energy of 250 MeV in the gantry rooms with different angles with respect to the patient; a fixed 250 MeV proton beam was also modeled. The ambient dose equivalent was calculated in several locations of interest inside and outside the facility, for different scenarios. The simulation results were compared qualitatively to previous work on an existing facility bearing some similarities with the design under study, showing that the ambient dose equivalent ranges obtained are reasonable. The ambient dose equivalents, calculated by means of the Geant4 simulation, were compared to the Australian regulatory limits and showed that the new facility will not pose health risks for the public or staff, with a maximum equivalent dose rate equal to 7.9 mSv/y in the control rooms and maze exit areas and 1.3·10⁻¹ mSv/y close to the walls, outside the facility, under very conservative assumptions. This work represents the first neutron shielding verification analysis of a new projected proton therapy facility and, as such, it may serve as a new source of comparison and validation for the international community, besides confirming the viability of the project from a radioprotection point of view.     

Geometry optimisation of graphite energy degrader for proton therapy

Introduction: Cyclotron-based proton therapy facilities use an energy degrader of variable thickness to deliver beams of the different energies required by a patient treatment plan; scattering and straggling in the degrader give rise to an inherent emittance increase and subsequent particle loss in the downstream energy-selection system (ESS). Here we study alternative graphite degrader geometries and examine with Monte-Carlo simulations the induced emittance growth and consequent particle transmission.Methods: We examined the conventional multiple-wedge degrader used in the Paul Scherrer Institute PROSCAN proton therapy system, the equivalent parallel-sided degrader, and a single block degrader of equivalent thickness. G4Beamline Monte-Carlo tracking of protons was benchmarked against measurements of the existing degrader for proton energies from 75 to 230 MeV, and used to validate simulations of the alternative geometries.Results: Using a careful calculation of the beam emittance growth, we determined that a single-block degrader placed close to the collimators of the ESS is expected to deliver significantly larger transmission, up to 17% larger at 150 MeV. At the lowest deliverable of 75 MeV there is still a clear improvement in beam transmission.Conclusions: Whilst dose rates are not presently limited on the PROSCAN system at higher energies, a single-block degrader offers the ability to access either lower energies for treatment or a larger dose rate at 75 MeV in case transmission optimisation is desired. Single-block degraders should be considered for the delivery of low-energy protons from a cyclotron-based particle therapy system.     

GEANT4 models for the secondary radiation flux in the collimation system of a 300 MeV proton microbeam

In Harbin, we are developing a 300 MeV proton microbeam for many applications in space science including upset studies in microelectronic devices, radiation hardness of materials for satellites and radiation effects in human tissues. There are also applications of this facility proposed for proton therapy. The microbeam system will employ a purpose-built proton synchrotron to provide the beam. However there are many challenges to be addressed in the design, construction and operation of this facility. Here we address two important design aspects for which we apply GEANT4 modeling. First, the high energy proton beam interacts strongly with beam line materials, especially the collimation slits, to produce showers of secondary particles which could introduce significant background signals and degrade the resolution of the proton microbeam. Second, the beam transport within the residual vacuum of the beam line may also introduce undesirable background radiation. In both cases mitigation strategies need to be incorporated during the design phase of the new system. We study the use of a dipole magnet following the aperture collimator to reduce the flux of secondary particles incident on the analysis chamber. Monte Carlo simulations are performed using GEANT4 and SRIM. By inserting the dipole magnet, we find as expected a significant reduction in the scattering of protons and other particles, such as neutrons and gamma rays, at the collimation system exit position. Secondary radiation from the residual gas pressure within the beam line vacuum system are also modelled and found to be negligible under the standard operating conditions.     

First biological images with high-energy proton microscopy

High-energy proton microscopy provides unique capabilities in penetrating radiography including the combination of high spatial resolution and field-of-view, dynamic range of density for measurements, and reconstructing density variations to less than 1% inside volumes and in situ environments. We have recently proposed to exploit this novel proton radiography technique for image-guided stereotactic particle radiosurgery. Results of a first test for imaging biological and tissue-equivalent targets with high-energy (800 MeV) proton microscopy are presented here. Although we used a proton microscope setup at ITEP (Moscow, Russia) optimized for fast dynamic experiments in material research, we could reach a spatial resolution of 150 μm with approximately 10¹⁰ protons per image. The potential of obtaining high-resolution online imaging of the target using a therapeutic proton beam in the GeV energy region suggests that high-energy proton microscopy may be used for image-guided proton radiosurgery.     

Experimental assessment of proton dose calculation accuracy in inhomogeneous media

PurposeProton therapy with Pencil Beam Scanning (PBS) has the potential to improve radiotherapy treatments. Unfortunately, its promises are jeopardized by the sensitivity of the dose distributions to uncertainties, including dose calculation accuracy in inhomogeneous media. Monte Carlo dose engines (MC) are expected to handle heterogeneities better than analytical algorithms like the pencil-beam convolution algorithm (PBA). In this study, an experimental phantom has been devised to maximize the effect of heterogeneities and to quantify the capability of several dose engines (MC and PBA) to handle these.MethodsAn inhomogeneous phantom made of water surrounding a long insert of bone tissue substitute (1 × 10 × 10 cm³) was irradiated with a mono-energetic PBS field (10 × 10 cm²). A 2D ion chamber array (MatriXX, IBA Dosimetry GmbH) lied right behind the bone. The beam energy was such that the expected range of the protons exceeded the detector position in water and did not attain it in bone. The measurement was compared to the following engines: Geant4.9.5, PENH, MCsquare, as well as the MC and PBA algorithms of RayStation (RaySearch Laboratories AB).ResultsFor a γ-index criteria of 2%/2 mm, the passing rates are 93.8% for Geant4.9.5, 97.4% for PENH, 93.4% for MCsquare, 95.9% for RayStation MC, and 44.7% for PBA. The differences in γ-index passing rates between MC and RayStation PBA calculations can exceed 50%.ConclusionThe performance of dose calculation algorithms in highly inhomogeneous media was evaluated in a dedicated experiment. MC dose engines performed overall satisfactorily while large deviations were observed with PBA as expected.     

Evaluation of energy deposition and secondary particle production in proton therapy of brain using a slab head phantom

AimEvaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy.BackgroundRadiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak.Materials and methodsA slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code.ResultsBy using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined.ConclusionsIt was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy “leaked” from the head by secondary photons and neutrons to be around 1%.     

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy

PurposeIn scattering proton therapy, the beam incidence, i.e. the patient’s orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature.MethodsMCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size.ResultsUsing a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63 μGy Gy⁻¹ and 149 μGy Gy⁻¹ were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient’s orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5 times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence.ConclusionBeam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient.     

Improvement on the yield of polyhydroxyalkanotes production from cheese whey by a recombinant Escherichia coli strain using the proton suicide methodology

In this work Escherichia coli strain CML3-1 was engineered through the insertion of Cupriavidus necator P(3HB)-synthesis genes, fused to a lactose-inducible promoter, into the chromosome, via transposition-mediated mechanism. It was shown that polyhydroxyalkanotes (PHAs) production by this strain, using cheese whey, was low due to a significant organic acids (OA) synthesis. The proton suicide method was used as a strategy to obtain an E. coli mutant strain with a reduced OA-producing capacity, aiming at driving bacterial metabolism toward PHAs synthesis.Thirteen E. coli mutant strains were obtained and tested in shake flask assays, using either rich or defined media supplemented with lactose. P8-X8 was selected as the best candidate strain for bioreactor fed-batch tests using cheese whey as the sole carbon source. Although cell growth was considerably slower for this mutant strain, a lower yield of OA on substrate (0.04 Cmol_OA/Cmol_lac) and a higher P(3HB) production (18.88 g_P(3HB)/L) were achieved, comparing to the original recombinant strain (0.11 Cmol_OA/Cmol_lac and 7.8 g_P(3HB)/L, respectively). This methodology showed to be effective on the reduction of OA yield by consequently improving the P(3HB) yield on lactose (0.28 Cmol_P(3HB)/Cmol_lac vs 0.10 Cmol_P(3HB)/Cmol_lac of the original strain).     

Allosteric interactions and proton conducting pathways in proton pumping aa3 oxidases: Heme a as a key coupling element

In this paper allosteric interactions in protonmotive heme aa₃ terminal oxidases of the respiratory chain are dealt with. The different lines of evidence supporting the key role of H⁺/e^? coupling (redox Bohr effect) at the low spin heme a in the proton pump of the bovine oxidase are summarized. Results are presented showing that the I-R54M mutation in P. denitrificans aa₃ oxidase, which decreases by more than 200 mV the E_m of heme a, inhibits proton pumping. Mutational aminoacid replacement in proton channels, at the negative (N) side of membrane-inserted prokaryotic aa₃ oxidases, as well as Zn^2 + binding at this site in the bovine oxidase, uncouples proton pumping. This effect appears to result from alteration of the structural/functional device, closer to the positive, opposite (P) surface, which separates pumped protons from those consumed in the reduction of O₂ to 2 H₂O. This article is part of a Special Issue entitled: Respiratory Oxidases.     

The relationship between cancer detection in mammography and image quality measurements

PurposeTo investigate the relationship between image quality measurements and the clinical performance of digital mammographic systems.MethodsMammograms containing subtle malignant non-calcification lesions and simulated malignant calcification clusters were adapted to appear as if acquired by four types of detector. Observers searched for suspicious lesions and gave these a malignancy score. Analysis was undertaken using jackknife alternative free-response receiver operating characteristics weighted figure of merit (FoM). Images of a CDMAM contrast-detail phantom were adapted to appear as if acquired using the same four detectors as the clinical images. The resultant threshold gold thicknesses were compared to the FoMs using a linear regression model and an F-test was used to find if the gradient of the relationship was significantly non-zero.ResultsThe detectors with the best image quality measurement also had the highest FoM values. The gradient of the inverse relationship between FoMs and threshold gold thickness for the 0.25 mm diameter disk was significantly different from zero for calcification clusters (p = 0.027), but not for non-calcification lesions (p = 0.11). Systems performing just above the minimum image quality level set in the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis resulted in reduced cancer detection rates compared to systems performing at the achievable level.ConclusionsThe clinical effectiveness of mammography for the task of detecting calcification clusters was found to be linked to image quality assessment using the CDMAM phantom. The European Guidelines should be reviewed as the current minimum image quality standards may be too low.