A possible dose enhancement effect by proton or electron irradiation in the vicinity of nanoparticles consisting of different high Z atomic materials has been investigated using the track structure ...Monte Carlo code TRAX. In the simulations, Fe, Ag, Gd, Pt and Au nanoparticles (r = 22 and 2 nm) were irradiated with monoenergetic proton beams at energies of therapeutic interest (2, 80 and 300 MeV) and 44 keV electrons. Due to the large number of electrons in atoms with high atomic numbers, many electrons can be released in Auger cascades in addition to the primary ionization process. The potential additional nanoscopic radial dose contributions in the presence of metallic nanoparticles are assessed by comparison with liquid water and water simulated with the same density as the metallic materials. We find a noticeable impact of Auger electrons emitted from the nanoparticles. Special focus has been given to the assessment of complete sets of low-energy electron cross sections for the nanoparticle materials.
Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, 16O ions are being widely discussed due to their increased LET ...distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with 16O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from 20 up to 750 keV μm−1, oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, 16O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to 12C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where 16O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of 0.15% or lower) and relatively low doses ( 4 Gy or lower) the choice of 16O over 12C or 4He may be justified.
We report on a novel method for simultaneous biological optimization of treatment plans for hypoxic tumors using multiple ion species. Our previously introduced kill painting approach, where the ...overall cell killing is optimized on biologically heterogeneous targets, was expanded with the capability of handling different ion beams simultaneously. The current version (MIBO) of the research treatment planning system TRiP98 has now been augmented to handle 3D (voxel-by-voxel) target oxygenation data. We present a case of idealized geometries where this method can identify optimal combinations leading to an improved peak-to-entrance effective dose ratio. This is achieved by the redistribution of particle fluences, when the heavier ions are preferentially forwarded to hypoxic target areas, while the lighter ions deliver the remaining dose to its normoxic regions. Finally, we present an in silico skull base chordoma patient case study with a combination of 4He and 16O beams, demonstrating specific indications for its potential clinical application. In this particular case, the mean dose, received by the brainstem, was reduced by 3%-5% and by 10%-12% as compared to the pure 4He and 16O plans, respectively. The new method allows a full biological optimization of different ion beams, exploiting the capabilities of actively scanned ion beams of modern particle therapy centers. The possible experimental verification of the present approach at ion beam facilities disposing of fast ion switch is presented and discussed.
High-Z material nanoparticles are being studied as localized dose enhancers in radiotherapeutic applications. Here, the nano-scale physical dose enhancement of proton, carbon and oxygen ion beam ...radiation by gold nanoparticles was studied by means of Monte Carlo track structure simulation with the TRAX code. We present 2D distributions and radial profiles of the additional dose and the dose enhancement factor for two geometries which consider an isolated and a water-embedded nanoparticle, respectively. Different nanoparticle sizes (radius of 1.2-22 nm) were found to yield qualitatively different absolute and relative dose enhancement distributions and different maximum dose enhancement factors (up to 20). Whereas the smallest nanoparticles produced the highest local dose enhancement factor close to the metal, larger ones led to lower, more diffuse dose enhancement factors that contributed more at larger distances. Differential absorption effects inside the metal were found to be responsible for those characteristics. For the energy range 15-204 MeVu−1, also a mild trend with ion E/A, regardless of the ion species, was found for embedded nanoparticles. In analogy to the width of the ion track itself, slower ions increased the enhancement at the nanoparticle surface. In contrast, no dependence on linear energy transfer was encountered. For slower ions (3-10 MeVu−1), the enhancement effect began to break down over all distances. Finally, the significance of any indirect physical effect was excluded, giving important hints especially in view of the low probabilities (at realistic concentrations and fluences) of direct ion-NP-hits. The very localized nature of the physical dose enhancement found suggests a strong action upon targets closeby, but no relevant effect at cellular distances. When pondering different possible damage enhancement mechanisms of gold nanoparticles in the context of published in vitro and in vivo experimental results, biological pathways are likely to play the key role.
On the robustness of the ammonia thermometer Maret, S.; Faure, A.; Scifoni, E. ...
Monthly Notices of the Royal Astronomical Society,
10/2009, Letnik:
399, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Ammonia inversion lines are often used as probes of the physical conditions in the dense interstellar medium. The excitation temperature between the first two para-metastable (rotational) levels is ...an excellent probe of the gas kinetic temperature. However, the calibration of this ammonia thermometer depends on the accuracy of the collisional rates with H2. Here, we present new collisional rates for ortho- and para-NH3 colliding with para-H2(J= 0), and investigate the effects of these new rates on the excitation of ammonia. Scattering calculations employ a new, high-accuracy, potential energy surface computed at the coupled-cluster CCSD(T) level with a basis set extrapolation procedure. Rates are obtained for all transitions involving ammonia levels with J≤ 3 and for kinetic temperatures in the range 5–100 K. We find that the calibration curve of the ammonia thermometer – which relates the observed excitation temperature between the first two para-metastable levels to the gas kinetic temperature – does not change significantly when these new rates are used. Thus, the calibration of ammonia thermometer appears to be robust. Effects of the new rates on the excitation temperature of inversion and rotation–inversion transitions are also found to be small.
In the present paper we numerically investigate, using Monte Carlo simulation, the theoretical results predicted by the Generalized Stochastic Microdosimetric Model (GSM2), as shown in the published ...companion paper. Taking advantage of the particle irradiation data ensemble (PIDE) dataset, we calculated GSM2 biological parameters of human salivary gland (HSG) and V79 cell lines. Further, exploiting the TOPAS-microdosimetric extension, we simulated the microdosimetric spectra of different radiation fields of therapeutic interest generated by four different ions (protons, helium-4, carbon-12 and oxygen-16) each at three different residual ranges. We investigated the properties of the initial damage distributions as well as the cell survival curve predicted by GSM2, focusing especially on the non-Poissonian effects naturally included in the model. GSM2 successfully computed cell survival curves, accurately describing experimental behavior even under challenging LET and dose conditions.
Relative biological effectiveness (RBE) variations are thought to be one of the primary causes of unexpected normal-tissue toxicities during tumor treatments with charged particles. Unlike carbon ...therapy, where treatment planning is optimized on the basis of the RBE-weighted dose, a constant RBE value of 1.1 is currently used in proton therapy. Assuming a uniform value can lead to under- or over-dosage, not just to the tumor but also to surrounding normal tissue. RBE changes have been linked with dose/fraction, the biological endpoint and beam properties. Understanding radiation quality and the associated RBE can improve the prediction of normal-tissue toxicities. In this study, we exploited microdosimetry for characterizing radiation quality in proton therapy in-field, and off-beam at 20 (beam edge), 50 (close out-of-field) and 100 (far out-of-field) mm from the beam center. We measured the lineal energy y spectra in a water phantom irradiated with 152 MeV protons, from which beam quality as well as the physical dose could be obtained. Taking advantage of the linear quadratic model and a modified version of the microdosimetric kinetic model, the microdosimetric data were combined with radiobiological parameters (α and β) of human salivary gland tumor cells for assessing cell survival RBE and RBE-weighted dose. The results indicate that if a dose of 60 Gy is delivered to the peak, the beam edge receives up to 6 Gy while the close and far out-of-field regions receive doses on the order of 10−3 Gy and 10−4 Gy, respectively. The RBE estimate in-beam shows large variations, ranging from 1.0 ± 0.2 at the entrance channel to 2.51 ± 0.15 at the tail. The beam edge follows a similar trend but the RBE calculated at the Bragg peak depth is 2.27 ± 0.17, i.e. twice the RBE in-beam (1.05 ± 0.15). Out-of-field, the estimated RBE is always significantly higher than 1.1 and increases with increasing lateral distance, reaching the overall highest value of 3.4 ± 0.3 at a depth of 206 mm and a lateral distance of 10 mm. The combination of RBE and dose into the biological dose points to the beam edge and the end-of-range in-beam as the areas with the highest risk of potential toxicities.
As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these ...facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics.
Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106–109 particles/s down to 101–105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.
We present a method for adapting a biologically optimized treatment planning for particle beams to a spatially inhomogeneous tumor sensitivity due to hypoxia, and detected e.g., by PET functional ...imaging. The TRiP98 code, established treatment planning system for particles, has been extended for including explicitly the oxygen enhancement ratio (OER) in the biological effect calculation, providing the first set up of a dedicated ion beam treatment planning approach directed to hypoxic tumors, TRiP-OER, here reported together with experimental tests. A simple semi-empirical model for calculating the OER as a function of oxygen concentration and dose averaged linear energy transfer, generating input tables for the program is introduced. The code is then extended in order to import such tables coming from the present or alternative models, accordingly and to perform forward and inverse planning, i.e., predicting the survival response of differently oxygenated areas as well as optimizing the required dose for restoring a uniform survival effect in the whole irradiated target. The multiple field optimization results show how the program selects the best beam components for treating the hypoxic regions. The calculations performed for different ions, provide indications for the possible clinical advantages of a multi-ion treatment. Finally the predictivity of the code is tested through dedicated cell culture experiments on extended targets irradiation using specially designed hypoxic chambers, providing a qualitative agreement, despite some limits in full survival calculations arising from the RBE assessment. The comparison of the predictions resulting by using different model tables are also reported.
In protontherapy, it has been suggested that nanoparticles of high-Z material like gold (GNP) could be used as radiosensitizers. The origin of this enhancement phenomenon for proton radiation is not ...yet well understood and additional mechanistic insights are required. Previous works have highlighted the good capabilities of TRAX to reproduce secondary electron emission from gold material. Therefore, TRAX cross sections obtained with the binary encounter approximation (BEA) model for proton ionization were implemented within Geant4 for gold material. Based on the TRAX cross sections, improved Geant4 simulations have been developed to investigate the energy deposition and radical species production around a spherical gold nanoparticle (5 and 10 nm in diameter) placed in a water volume during proton irradiation. Simulations were performed for incident 2 MeV proton. The dose enhancement factor and the radiolysis enhancement factor were quantified. Results obtained with the BEA model were compared with results obtained with condensed-history models. Experimental irradiation of 200 nm gold films were performed to validate the secondary electron emission reproduction capabilities of physical models used in Monte Carlo (MC) simulations. TRAX simulations reproduced the experimental backscattered electron energy spectrum from gold film with better agreement than Geant4. Results on gold film obtained with the BEA model enabled to estimate the electron emission from GNPs. Results obtained in our study tend to support that the use of the BEA discrete model leads to a significant increase of the dose in the near vicinity of GNPs (<20 nm), while condensed history models used in Geant4 seem to overestimate the dose and the number of chemical species for increasing distances from the GNP. Based on discrete BEA model results, no enhancement effect due to secondary electron emitted from the GNP is expected if the GNP is not in close proximity to key cellular functional elements (DNA, mitochondria...).
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