Measurement of the

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.

74 Ge( n , γ ) cross section below 70 keV measured at n_TOF CERN.

Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.

Neutron Capture on the s-Process Branching Point

The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass A∼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the A∼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.

Experimental validation of an analytical microdosimetric model based on Geant4-DNA simulations by using a silicon-based microdosimeter.

PURPOSE: To study the agreement between proton microdosimetric distributions measured with a silicon-based cylindrical microdosimeter and a previously published analytical microdosimetric model based on Geant4-DNA in-water Monte Carlo simulations for low energy proton beams. METHODS AND MATERIAL: Distributions for lineal energy (y) are measured for four proton monoenergetic beams with nominal energies from 2.0 MeV to 4.5 MeV, with a tissue equivalent proportional counter (TEPC) and a silicon-based microdosimeter. The actual energy for protons traversing the silicon-based microdosimeter is simulated with SRIM. Monoenergetic beams with these energies are simulated with Geant4-DNA code by simulating a water cylinder site of dimensions equal to those of the microdosimeter. The microdosimeter response is calibrated by using the distribution peaks obtained from the TEPC. Analytical calculations for y ¯ F and y ¯ D using our methodology based on spherical sites are also performed choosing the equivalent sphere to be checked against experimental results. RESULTS: Distributions for y at silicon are converted into tissue equivalent and compared to the Geant4-DNA simulated, yielding maximum deviations of 1.03% for y ¯ F and 1.17% for y ¯ D . Our analytical method generates maximum deviations of 1.29% and 3.33%, respectively, with respect to experimental results. CONCLUSION: Simulations in Geant4-DNA with ideal cylindrical sites in liquid water produce similar results to the measurements in an actual silicon-based cylindrical microdosimeter properly calibrated. The found agreement suggests the possibility to experimentally verify the calculated clinical y ¯ D with our analytical method.

Neutron capture cross section of unstable 63Ni: implications for stellar nucleosynthesis.

The 63Ni(n,γ) cross section has been measured for the first time at the neutron time-of-flight facility n_TOF at CERN from thermal neutron energies up to 200 keV. In total, capture kernels of 12 (new) resonances were determined. Maxwellian averaged cross sections were calculated for thermal energies from kT=5-100 keV with uncertainties around 20%. Stellar model calculations for a 25M⊙ star show that the new data have a significant effect on the s-process production of 63Cu, 64Ni, and 64Zn in massive stars, allowing stronger constraints on the Cu yields from explosive nucleosynthesis in the subsequent supernova.

Implementation of the microdosimetric kinetic model using analytical microdosimetry in a treatment planning system for proton therapy.

PURPOSE: To implement RBE calculations in treatment planning systems based on the Microdosimetric Kinetic Model (MKM) upon analytical calculations of dose-mean lineal energy (yD). MKM relies on the patterns of energy deposition in sub-nuclear structures called domains, whose radii are cell-specific and need to be determined. METHODS AND MATERIAL: The radius of a domain (rd) can be determined from the linear-quadratic (LQ) curves from clonogenic experiments for different cell lines exposed to X-ray and proton beams with known yD. In this work, LQ parameters for two different human lung cell lines (H1299 and H460) are used, and yD among cells is calculated through an analytical algorithm. Once rd is determined, MKM-based calculations of RBE are implemented in a treatment planning system (TPS). Results are compared to those produced by phenomenological models of RBE, such as Carabe and McNamara. RESULTS: Differences between model-based predictions and experimentally determined RBE are analyzed for yD=5 keV/µm. For the H1299 line, mean differences in RBE are 0.13, -0.29 and -0.27 for our MKM-based calculation, Carabe and McNamara models, respectively. For the H460 line, differences become -0.044, -0.091 and -0.048, respectively. RBE is computed for these models in a simple plan, showing MKM the best agreement with the experimentally obtained RBE, keeping deviations below 0.08. CONCLUSIONS: Microdosimetry calculations at the TPS-level provide tools to improve predictions of RBE using the MKM with actual values of yD instead of LET. The radius of the characteristic domain needs to be determined to tailor the RBE prediction for each cell or tissue.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

An Analytical Microdosimetric Model for Radioimmunotherapeutic Alpha Emitters.

In this work, we present a methodology to analytically determine microdosimetric quantities in radioimmunotherapy and targeted radiotherapy with alpha particles. Monte Carlo simulations using the Geant4-DNA toolkit, which provides interaction models at the microscopic level, are performed for monoenergetic alpha particles traversing spherical sites with diameters of 1, 5 and 10 µm. An analytical function is fitted against the data in each case to model the energy imparted by monoenergetic particles to the site, as well as the variance of the distribution of energy imparted. Those models allow us to obtain the mean and dose-mean values of specific energy (z) and lineal energy (y) for polyenergetic arrangements of alpha particles. The energetic spectrum is estimated by considering the distance that each particle needs to travel to reach the sensitive target. We apply this methodology to a simple case in radioimmunotherapy: a spherical cell that has its membrane uniformly covered by 211At, an alpha emitter, with a spherical target representing the nucleus, placed at the center of the cell. We compare the results of our analytical method with calculations using Geant4-DNA of this specific setup for three nucleus sizes corresponding to our three functions. For nuclei with diameter of 1 µm and 5 µm, all mean and dose-mean quantities for y and z were in an agreement within 4% to Geant4-DNA calculations. This agreement improves to approximately 1% for dose-mean lineal energy and dose-mean specific energy. For the 10-µm-diameter case, discrepancies scale to approximately 9% for mean values and 3% for dose-mean values. Dose-mean values are within Geant4-DNA uncertainties in all cases. Our method provides accurate analytical calculations of dose-mean quantities that may be further employed to characterize radiobiological effectiveness of targeted radiotherapy. The spatial distributions of sources and targets are required to calculate microdosimetric-relevant quantities.

On the concepts of dose-mean lineal energy, unrestricted and restricted dose-averaged LET in proton therapy.

To calculate 3D distributions of microdosimetric-based restricted dose-averaged LET (LETd) and dose-mean lineal energy ([Formula: see text]) in order to explore their similarities and differences between each other and with the traditional unrestricted LETd. Additionally, a new expression for optimum restricted LETd calculation is derived, allowing for disregarding straggling-associated functions in the classical microdosimetric theory. Restricted LETd and [Formula: see text] for polyenergetic beams can be obtained by integrating previously developed energy-dependent microdosimetric functions over the energetic spectrum of these beams. This calculation is extended to the entire calculation volume using an algorithm to determine spectral fluence. Equivalently, unrestricted LETd can be obtained integrating the stopping power curve on the spectrum. A new expression to calculate restricted LETd is also derived. Results for traditional and new formulas are compared for a clinical 100 MeV proton beam. Distributions of unrestricted LETd, restricted LETd and [Formula: see text] are analyzed for a prostate case, for microscopic spherical sites of 1 µm and 10 µm in diameter. Traditional and new expressions for restricted LETd remarkably agree, being the mean differences 0.05 ± 0.04 keV µm-1 for the 1 µm site and 0.05 ± 0.02 keV µm-1 for the 10 µm site. In the prostate case, the ratio between the maximum and the central value for central axis (CAX) profiles is around 2 for all the quantities, being the highest for restricted LETd for 1 µm (2.17) and the lowest for [Formula: see text] for 1 µm (1.78). Unrestricted LETd, restricted LETd and [Formula: see text] can be analytically computed and compared for clinical plans. Two important consequences of the calculation of [Formula: see text] are: (1) its distribution can be verified by directly measuring it in clinical beams; and (2), optimization of proton treatments based on these quantities is enabled as well as future developments of RBE models based on them.

A kernel-based algorithm for the spectral fluence of clinical proton beams to calculate dose-averaged LET and other dosimetric quantities of interest.

PURPOSE: To introduce a new analytical methodology to calculate quantities of interest in particle radiotherapy inside the treatment planning system. Models are proposed to calculate dose-averaged LET (LETd) in proton radiotherapy. MATERIAL AND METHODS: A kernel-based approach for the spectral fluence of particles is developed by means of analytical functions depending on depth and lateral position. These functions are obtained by fitting them to data calculated with Monte Carlo (MC) simulations using Geant4 in liquid water for energies from 50 to 250 MeV. Contributions of primary, secondary protons and alpha particles are modeled separately. Lateral profiles and spectra are modeled as Gaussian functions to be convolved with the fluence coming from the nozzle. LETd is obtained by integrating the stopping power curves from the PSTAR and ASTAR databases weighted by the spectrum at each position. The fast MC code MCsquare is employed to benchmark the results. RESULTS: Considering the nine energies simulated, fits for the functions modeling the fluence in-depth provide an average R 2 equal to 0.998, 0.995 and 0.986 for each one of the particles considered. Fits for the Gaussian lateral functions yield average R 2 of 0.997, 0.982 and 0.993, respectively. Similarly, the Gaussian functions fitted to the computed spectra lead to average R 2 of 0.995, 0.938 and 0.902. LETd calculation in water shows mean differences of -0.007 ± 0.008 keV/µm with respect to MCsquare if only protons are considered and 0.022 ± 0.007 keV/µm including alpha particles. In a prostate case, mean difference for all voxels with dose >5% of prescribed dose is 0.28 ± 0.23 keV/µm. CONCLUSION: This new spectral fluence-based methodology allows for simultaneous calculations of quantities of interest in proton radiotherapy such as dose, LETd or microdosimetric quantities. The method also enables the inclusion of more particles by following an analogous process.

Segment-averaged LET concept and analytical calculation from microdosimetric quantities in proton radiation therapy.

PURPOSE: This work introduces the concept of segment-averaged linear energy transfer (LET) as a new approach to average distributions of LET of proton beams based on a revisiting of microdosimetry theory. The concept of segment-averaged LET is then used to generate an analytical model from Monte Carlo simulations data to perform fast and accurate calculations of LET distributions for proton beams. METHODS AND MATERIAL: The distribution of energy imparted by a proton beam into a representative biological structure or site is influenced by the distributions of (a) LET, (b) segment length, which is the section of the proton track in the site, and (c) energy straggling of the proton beam. The distribution of LET is thus generated by the LET of each component of the beam in the site. However, the situation when the LET of each single proton varies appreciably along its path in the site is not defined. Therefore, a new distribution can be obtained if the particle track segment is decomposed into smaller portions in which LET is roughly constant. We have called "segment distribution" of LET the one generated by the contribution of each portion. The average of that distribution is called segment-averaged LET. This quantity is obtained in the microdosimetry theory from the average and standard deviation of the distributions of energy imparted to the site, segment length, and energy imparted per collision. All this information is calculated for protons of clinically relevant energies by means of Geant4-DNA microdosimetric simulations. Finally, a set of analytical functions is proposed for each one of the previous quantities. The presented model functions are fitted to data from Geant4-DNA simulations for monoenergetic beams from 100 keV to 100 MeV and for spherical sites of 1, 5, and 10 µm in diameter. RESULTS: The average differences along the considered energy range between calculations based on our analytical models and MC for segment-averaged dose-averaged restricted LET are -0.2 ± 0.7 keV/µm for the 1 µm case, 0.0 ± 0.9 keV/µm for the 5 µm case, and -0.3 ± 1.1 keV/µm for the 10 µm case, respectively. All average differences are below the average standard deviation (1σ) of the MC calculations. CONCLUSIONS: A new way of averaging LET for a proton beam is performed to incorporate the effects produced by the variation of stopping power of each individual proton along microscopic biological structures. An analytical model based on MC simulations allows for fast and accurate calculations of segment-averaged dose-averaged restricted LET for proton beams, which otherwise would need to be calculated from exhaustive MC simulations of clinical plans.

Dose-averaged LET calculation for proton track segments using microdosimetric Monte Carlo simulations.

PURPOSE: There is an increasing interest in calculating linear energy transfer (LET) distributions for proton therapy treatments in order to assess the influence of this quantity in biological terms. Microdosimetric Monte Carlo (MC) simulations are useful tools to calculate dose-averaged LET, as this has been broadly proposed as the most adequate quantity to characterize these biological effects. However, a straightforward uniform sampling of the scoring site turns out to be computationally unaffordable. In contrast, some issues have been pointed out with the more efficient weighted sampling approach, frequently used in literature. Here, we address the issues associated with the latter method and propose adequate corrections to achieve reliable calculations of dose-averaged LET values from microdosimetry. METHODS AND MATERIALS: Proton track structures have been simulated with Geant4-DNA considering two different approaches. One version employs a uniform sampling for placing the spherical site and is used as the reference. The other one uses a weighted sampling by considering the spatial distribution of transfer points. Some corrections are proposed for calculating a dose-averaged LET comparable to the reference case. An additional MC approach is proposed to obtain the weighted mean of the energy imparted per electronic collision of the proton within the site, the δ 2 function, related to the straggling distribution, as an intermediate step in the LET calculation. RESULTS: Energy imparted per event distributions are different when employing either sampling methods, due to the different geometrical randomness. We have found an agreement below (0.15 ± 0.05) keV/µm in the worst case for uniform and weighted methods in dose-averaged LET values when the weighted sampling results are corrected according to our proposal. Our analysis is restricted to spherical sites of 1 and 10 µm diameter and monoenergetic beams in the range from 2 to 90 MeV. CONCLUSIONS: This work shows a reliable and computational-efficient method to perform calculations of track segment dose-averaged LET using MC simulations for proton therapy beams, including the necessary considerations for obtaining the straggling distribution characteristics. The validity of this approach remains as long as the stopping power of the proton can be considered as constant along its track within the site.

Dosimetric impact assessment using a general algorithm in geant4 simulations for a complex-shaped multileaf collimator.

PURPOSE: We have developed an inhouse algorithm for the multileaf collimator (MLC) geometry model construction with an appropriate accuracy for dosimetric tests. Our purpose is to build a complex type of MLC and analyze the influence of the modeling parameters on the dose calculation. METHODS: Using radiochromic films as detector the following tests were done: (I) Density test field: to compare measured and calculated dose distributions in order to determine the tungsten alloy physical density value. (II) Leaf ends test field: to verify the penumbra shape sensitivity against the discretization level set to simulate the curved leaf ends. (III) MLC-closed field: to obtain the value of the air gap between opposite leaves for a closed configuration which completes the modeling of the MLC leakage radiation. (IV) Picket-fence field: to fit the leaf tilt angle with respect of the divergent ray emerging from the source. RESULTS: For a 18.5g/cm3 density value we have obtained a maximum, minimum and mean leakage values of 0.43%, 0.36% and 0.38%, similar to the experimental ones. The best discretization level in the leaf ends field shows a 5.51mm FWHM, very close to the measured value (5.49mm). An air gap of 370µm has been used in the simulation for the separation between opposite leaves. Using a 0.44° tilt angle, we found the same pattern as the experimental values. CONCLUSIONS: Our code can reproduce complex MLC designs with a submilimetric dosimetric accuracy which implies the necessary background for dose calculation of high clinical interest small fields.

LabVIEW-based control and acquisition system for the dosimetric characterization of a silicon strip detector.

The aim of this work is to present a new data acquisition, control, and analysis software system written in LabVIEW. This system has been designed to obtain the dosimetry of a silicon strip detector in polyethylene. It allows the full automation of the experiments and data analysis required for the dosimetric characterization of silicon detectors. It becomes a useful tool that can be applied in the daily routine check of a beam accelerator.

Fragmentation of 120 and 200 MeV u-14He ions in water and PMMA targets.

Recently, the use of 4He particles in cancer radiotherapy has been reconsidered as they potentially represent a good compromise between protons and 12C ions. The first step to achieve this goal is the development of a dedicated treatment planning system, for which basic physics information such as the characterization of the beam lateral scattering and fragmentation cross sections are required. In the present work, the attenuation of 4He primary particles and the build-up of secondary charged fragments at various depths in water and polymethyl methacrylate were investigated experimentally for 120 and 200 MeV u-1 beams delivered by the synchrotron at the Heidelberg Ion-Beam Therapy Center, Heidelberg. Species and isotope identification was accomplished combining energy loss and time-of-flight measurements. Differential yields and energy spectra of all fragments types were recorded between 0° and 20° with respect to the primary beam direction.

Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons.

In order to integrate radiobiological modelling with clinical treatment planning for proton radiotherapy, we extended our in-house treatment planning system FoCa with a 3D analytical algorithm to calculate linear energy transfer (LET) in voxelized patient geometries. Both active scanning and passive scattering delivery modalities are supported. The analytical calculation is much faster than the Monte-Carlo (MC) method and it can be implemented in the inverse treatment planning optimization suite, allowing us to create LET-based objectives in inverse planning. The LET was calculated by combining a 1D analytical approach including a novel correction for secondary protons with pencil-beam type LET-kernels. Then, these LET kernels were inserted into the proton-convolution-superposition algorithm in FoCa. The analytical LET distributions were benchmarked against MC simulations carried out in Geant4. A cohort of simple phantom and patient plans representing a wide variety of sites (prostate, lung, brain, head and neck) was selected. The calculation algorithm was able to reproduce the MC LET to within 6% (1 standard deviation) for low-LET areas (under 1.7 keV µm(-1)) and within 22% for the high-LET areas above that threshold. The dose and LET distributions can be further extended, using radiobiological models, to include radiobiological effectiveness (RBE) calculations in the treatment planning system. This implementation also allows for radiobiological optimization of treatments by including RBE-weighted dose constraints in the inverse treatment planning process.

A critical study of different Monte Carlo scoring methods of dose average linear-energy-transfer maps calculated in voxelized geometries irradiated with clinical proton beams.

We compare unrestricted dose average linear energy transfer (LET) maps calculated with three different Monte Carlo scoring methods in voxelized geometries irradiated with proton therapy beams with three different Monte Carlo scoring methods. Simulations were done with the Geant4 (Geometry ANd Tracking) toolkit. The first method corresponds to a step-by-step computation of LET which has been reported previously in the literature. We found that this scoring strategy is influenced by spurious high LET components, which relative contribution in the dose average LET calculations significantly increases as the voxel size becomes smaller. Dose average LET values calculated for primary protons in water with voxel size of 0.2 mm were a factor ~1.8 higher than those obtained with a size of 2.0 mm at the plateau region for a 160 MeV beam. Such high LET components are a consequence of proton steps in which the condensed-history algorithm determines an energy transfer to an electron of the material close to the maximum value, while the step length remains limited due to voxel boundary crossing. Two alternative methods were derived to overcome this problem. The second scores LET along the entire path described by each proton within the voxel. The third followed the same approach of the first method, but the LET was evaluated at each step from stopping power tables according to the proton kinetic energy value. We carried out microdosimetry calculations with the aim of deriving reference dose average LET values from microdosimetric quantities. Significant differences between the methods were reported either with pristine or spread-out Bragg peaks (SOBPs). The first method reported values systematically higher than the other two at depths proximal to SOBP by about 15% for a 5.9 cm wide SOBP and about 30% for a 11.0 cm one. At distal SOBP, the second method gave values about 15% lower than the others. Overall, we found that the third method gave the most consistent performance since it returned stable dose average LET values against simulation parameter changes and gave the best agreement with dose average LET estimations from microdosimetry calculations.