Dose-averaged Lineal Energy Research Articles

Silicon 3D Microdetectors for Microdosimetry in Hadron Therapy.

The present overview describes the evolution of new microdosimeters developed in the National Microelectronics Center in Spain (IMB-CNM, CSIC), ranging from the first ultra-thin 3D diodes (U3DTHINs) to the advanced 3D-cylindrical microdetectors, which have been developed over the last 10 years. In this work, we summarize the design, main manufacture processes, and electrical characterization of these devices. These sensors were specifically customized for use in particle therapy and overcame some of the technological challenges in this domain, namely the low noise capability, well-defined sensitive volume, high spatial resolution, and pile-up robustness. Likewise, both architectures reduce the loss of charge carriers due to trapping effects, the charge collection time, and the voltage required for full depletion compared to planar silicon detectors. In particular, a 3D‒cylindrical architecture with electrodes inserted into the silicon bulk and with a very well‒delimited sensitive volume (SV) mimicked a cell array with shapes and sizes similar to those of mammalian cells for the first time. Experimental tests of the carbon beamlines at the Grand Accélérateur National d’Lourds (GANIL, France) and Centro Nazionale Adroterapia Oncologica (CNAO, Italy) showed the feasibility of the U3DTHINs in hadron therapy beams and the good performance of the 3D‒cylindrical microdetectors for assessing linear energy distributions of clinical beams, with clinical fluence rates of 5 × 107 s−1cm−2 without saturation. The dose-averaged lineal energies showed a generally good agreement with Monte Carlo simulations. The results indicated that these devices can be used to characterize the microdosimetric properties in hadron therapy, even though the charge collection efficiency (CCE) and electronic noise may pose limitations on their performance, which is studied and discussed herein. In the last 3D‒cylindrical microdetector generation, we considerably improved the CCE due to the microfabrication enhancements, which have led to shallower and steeper dopant profiles. We also summarize the successive microdosimetric characterizations performed with both devices in proton and carbon beamlines.

Nanodosimetric understanding to the dependence of the relationship between dose-averaged lineal energy on nanoscale and LET on ion species.

With the extension of ion species in ion-beam radiotherapy, the sole dependence of relative biological effectiveness (RBE) on linear energy transfer (LET) is insufficient when comparing RBE for ion beams with the same LET value. The aim of the present study was to provide a systematic study of the nanodosimetry for ion beams with the same LET value. Based on the calculated LET profiles of ion beams with range about 130mm, lineal energy spectra and dose-averaged lineal energy [Formula: see text] on 4nm site for various clinical ion beams were obtained. Then, the lineal energy spectra and [Formula: see text] values were compared for ion beams with the same LET values. The results showed that the relationships between [Formula: see text] and LET for various ion beams present an dependence on ion species. For ion beams with the same LET value, the ion beams with smaller nucleon number yielded greater [Formula: see text] values. The probability of the small-nucleon-number ion beams to generate large energy deposition events on nanoscale was higher than that of the large-nucleon-number ion beams. The dependence of the relationship between RBE and LET on ion species might be attributed to the fluctuation of energy depositions on nanometer scale.

Technical Note: Effect of magnetic fields on the microdosimetry of carbon-ion beams.

To investigate the influence of magnetic fields on the microdosimetry of carbon-ion beams and the scaling effect of tissue equivalent proportional counter (TEPC) defined as the change of energy deposition in a TEPC from that in a microscopic scale region of interest due to the presence of a magnetic field in combination with the TEPC larger physical dimensions. Geant4-based Monte Carlo simulations were conducted to calculate the microdosimetric quantities for carbon-ion beams with different initial energies (10-290MeV/u) under magnetic fields of various strengths (0.5-3T). The calculations were performed for a 1μm spherical volume made of tissue, and for spherical TEPCs of 1 and 10mm in diameter. Then, values of dose-averaged lineal energy (yD ) were acquired for the different scenarios to analyze the effect of magnetic fields on the microdosimetry of carbon-ion beams and the scaling effect of TEPC. The yD values and lineal energy spectra in the 1μm spherical tissue volume for the scenarios without magnetic field and with magnetic fields of different strengths and directions remained nearly the same for the various energy carbon-ion beams. However, compared with those of the 1μm spherical tissue volume, an increase of of yD values and an obvious shift of the lineal energy spectra for the TEPCs of 1 and 10mm in diameter under magnetic fields were found. The application of magnetic fields under 3T has no significant influence on the microdosimetric results of carbon-ion beams. However, there is definitely a scaling effect when using TEPC for microdosimetric study, which alters the reading of TEPC in the presence of magnetic fields. Novel methods to correct the reading of TEPC or scaling effect-resistant microdosimetric measurement detectors are urgently needed to perform experimental microdosimetric studies under magnetic fields.

Risk factors associated with intestinal permeability in an adult population: A systematic review

A TEPC capable of simulating site sizes down to 25 nm was designed and constructed in order to fill the gap between nanodosimetry and experimental microdosimetry. In this paper, this device was proposed for assessing the quality of the therapeutic CATANA (INFN-LNS) proton beam. The detector was irradiated with a modulated 62 MeV proton beam and was placed at different depths across the spread-out of Bragg peak. For each position, several microdosimetric distributions for different simulated site size from 0.5 μm to 35 nm were acquired. The 0.5 μm spectra are in good agreement with spectra measured employing a reference TEPC in the same experimental conditions. The results show that, for bigger sites, microdosimetric distributions follow the slowing down of the primary particles, while, for smaller sites, they exhibit a bimodal shape, in particular at smaller depths in PMMA. The comparison between different simulated volumes shows an increment of the dose-averaged lineal energy with the reduction of the site. Moreover, a comparison between a ratio of the dose-averaged lineal energy for different simulates site sizes and the microdosimetric RBE shows that the smaller is the simulated volume, the better is the resembling of the microdosimetric RBE even if, the agreement is not yet fully reached for any site size. Finally, Monte Carlo simulations show that the electron energy threshold in FLUKA is too high for reproducing microdosimetric distributions for nanometric sites for proton beams.

Nano-microdosimetric investigation at the therapeutic proton irradiation line of CATANA

A TEPC capable of simulating site sizes down to 25 nm was designed and constructed in order to fill the gap between nanodosimetry and experimental microdosimetry. In this paper, this device was proposed for assessing the quality of the therapeutic CATANA (INFN-LNS) proton beam. The detector was irradiated with a modulated 62 MeV proton beam and was placed at different depths across the spread-out of Bragg peak. For each position, several microdosimetric distributions for different simulated site size from 0.5 μm to 35 nm were acquired. The 0.5 μm spectra are in good agreement with spectra measured employing a reference TEPC in the same experimental conditions. The results show that, for bigger sites, microdosimetric distributions follow the slowing down of the primary particles, while, for smaller sites, they exhibit a bimodal shape, in particular at smaller depths in PMMA. The comparison between different simulated volumes shows an increment of the dose-averaged lineal energy with the reduction of the site. Moreover, a comparison between a ratio of the dose-averaged lineal energy for different simulates site sizes and the microdosimetric RBE shows that the smaller is the simulated volume, the better is the resembling of the microdosimetric RBE even if, the agreement is not yet fully reached for any site size. Finally, Monte Carlo simulations show that the electron energy threshold in FLUKA is too high for reproducing microdosimetric distributions for nanometric sites for proton beams.

Investigating Dependencies of Relative Biological Effectiveness for Proton Therapy in Cancer Cells.

Relative biological effectiveness (RBE) accounts for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1. In this work we investigated the RBE of protons and correlated the biological differences with the underlying physical quantities. Three cell lines were irradiated (CHO, Chinese hamster ovary; A549, human lung adenocarcinoma; and T98, human glioma) and assessed for cell survival by using clonogenic assay. Cells were irradiated with 71- and 160-MeV protons at depths along the Bragg curve and 6-MV photons to various doses. The dose-averaged lineal energy ( ) was measured under similar conditions as the cells by using a microdosimeter. Dose-averaged linear energy transfer (LETd) was also calculated by using Monte Carlo (MC) simulations. Survival data were fit by using the linear quadratic model. The RBE values were calculated by comparing the physical dose (D6MV/Dp) that results in 50% (RBE0.5) and 10% (RBE0.1) cell survival, and survival after 2 Gy (RBE2Gy). Proton RBE values ranged from 0.89 to 2.40. The RBE for all 3 cell lines increased with decreasing proton energy and was higher at 50% survival than at 10% survival. Additionally, both A549 and T98 cells generally had higher RBE values relative to the CHO cells, indicating a greater biological response to protons. An increase in RBE corresponded with an increase in and LETd. Proton RBE was found to depend on mean proton energy, survival end point, and cell type. Changes in both and LETd were also found to impact proton RBE values, but consideration of the energy spectrum may provide additional information. The RBE values in this study vary greatly, indicating the clinical value of 1.1 may not be suitable in all cases.

Abstract ID: 196 Relation between dose average linear energy transfer and dose mean lineal energy calculated for proton therapy beams off axis: A study with the Geant4 toolkit.

In a previous work we compared various methods to score, in a voxelized geometry, dose average linear energy transfer (LETd) distributions produced by proton therapy beams in water [1] . In that work, in order to determine which method provided more reliable results, we resorted to numerical stability against changes of geometry and production cuts, and to comparison against LETd values obtained from microdosimetry calculations according to a formula proposed in [2] . Our simulations, with which we could come up with a robust LETd computation method in good agreement with microdosimetry calculations, were done with the Geant4 toolkit [3] , [4] , [5] at central axis and for primary protons only. The aim of this work is to further prove the validity of the method, extending the calculation to off-axis voxels and including the contribution of secondary protons. With this purpose, we compared LETd distributions (2D) calculated for clinical proton beams with those computed from microdosimetry spectra obtained for sites of various sizes, whose typical dimension ranged from 0.25 to 10 microns. The microdosimetry calculations were done with the Geant4-DNA physics package, that simulates step by step interactions of particles in liquid water down to the eV scale [6] , [7] . Our preliminary results confirmed the overall validity of the method at increasing off-axis distances. However, we could also find a significant dependence on the site size of the deviations reported between our “macroscopic” LETd values and those obtained from microdosimetry calculations.

RADIATION PROTECTION MEASUREMENTS WITH THE VARIANCE-COVARIANCE METHOD IN THE STRAY RADIATION FIELDS FROM PHOTON AND PROTON THERAPY FACILITIES.

The microdosimetric variance-covariance method was used to study the stray radiation fields from the photon therapy facility at the Technical University of Denmark and the scanned proton therapy beam at the Skandion Clinic in Uppsala, Sweden. Two TEPCs were used to determine the absorbed dose, the dose-average lineal energy, the dose-average quality factor and the dose equivalent. The neutron component measured by the detectors at the proton beam was studied through Monte Carlo simulations using the code MCNP6. In the photon beam the stray absorbed dose ranged between 0.3 and 2.4 μGy per monitor unit, and the dose equivalent between 0.4 and 9 μSv per monitor unit, depending on beam energy and measurement position. In the proton beam the stray absorbed dose ranged between 3 and 135 μGy per prescribed Gy, depending on detector position and primary proton energy.

SU‐F‐T‐193: Evaluation of a GPU‐Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

Purpose:Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency.Methods:We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair‐misrepair‐fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS).Results:Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE‐weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster.Conclusion:Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE‐weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

COMPARISON STUDY OF VARIOUS PLASTICS AS THE WALL MATERIAL OF THGEM-BASED MICRODOSEMETERS FOR FAST NEUTRON MEASUREMENTS.

To find appropriate substitutions for the expensive plastics of A-150 and rexolite used in the construction of thick gas electron multiplier (THGEM)-based tissue-equivalent proportional counters, in the present work, the responses of a THGEM-based microdosimetric detector made of A-150 and rexolite and three others composed of plexiglas (PMMA), polyethylene and polystyrene plastics as the wall materials have been compared. Lineal energy distribution, frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent for 0.1, 1 and 10 MeV neutrons and also for 241Am-Be neutrons are calculated using Geant4 simulation toolkit. Frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent values for all plastics are found similar. In addition, the response of an indigenously constructed microdosemeter with PMMA walls is also measured for 241Am-Be neutrons. The experimental results are in good agreement with the simulation predictions. Conclusively, it was found that the three considered plastics can be used as good candidates instead of A-150 and rexolite plastics in fast neutron microdosimetry.

Microdosimetry of the full slowing down of protons using Monte Carlo track structure simulations.

The article investigates two approaches in microdosimetric calculations based on Monte Carlo track structure (MCTS) simulations of a 160-MeV proton beam. In the first approach, microdosimetric parameters of the proton beam were obtained using the weighted sum of proton energy distributions and microdosimetric parameters of proton track segments (TSMs). In the second approach, phase spaces of energy depositions obtained using MCTS simulations in the full slowing down (FSD) mode were used for the microdosimetric calculations. Targets of interest were water cylinders of 2.3-100 nm in diameters and heights. Frequency-averaged lineal energies ([Formula: see text]) obtained using both approaches agreed within the statistical uncertainties. Discrepancies beyond this level were observed for dose-averaged lineal energies ([Formula: see text]) towards the Bragg peak region due to the small number of proton energies used in the TSM approach and different energy deposition patterns in the TSM and FSD of protons.

Lineal energy and radiation quality in radiation therapy: model calculations and comparison with experiment

Microdosimetry is a recommended method for characterizing radiation quality in situations when the biological effectiveness under test is not well known. In such situations, the radiation beams are described by their lineal energy probability distributions. Results from radiobiological investigations in the beams are then used to establish response functions that relate the lineal energy to the relative biological effectiveness (RBE). In this paper we present the influence of the size of the simulated volume on the relation to the clinical RBE values (or weighting factors). A single event probability distribution of the lineal energy is approximated by its dose average lineal energy () which can be measured or calculated for volumes from a few micrometres down to a few nanometres. The clinical RBE values were approximated as the ratio of the α-values derived from the LQ-relation. Model calculations are presented and discussed for the SOBP of a 12C ion (290 MeV u−1) and the reference 60Co γ therapy beam. Results were compared with those for a conventional x-ray therapy beam, a 290 MeV proton beam and a neutron therapy beam. It is concluded that for a simulated volume of about 10 nm, the α-ratio increases approximately linearly with the -ratio for all the investigated beams. The correlation between y and α provides the evidence to characterize a radiation therapy beam by the lineal energy when, for instance, weighting factors are to be estimated.

Microdosimetric assessment of the radiation quality of a therapeutic proton beam: comparison between numerical simulation and experimental measurements

Using protons for the treatment of ocular melanoma (especially of posterior pole tumours), the radiation quality of the beam must be precisely assessed to preserve the vision and to minimise the damage to healthy tissue. The radiation quality of a therapeutic proton beam at the Centre Antoine Lacassagne in Nice (France) was measured using microdosimetric techniques, i.e. a miniaturised version of a tissue-equivalent proportional counter. Measurements were performed in a 1-µm site at different depths in a Lucite phantom. Experimental data showed a significant increase in the beam quality at the distal edge of the spread-out Bragg peak (SOBP). In this paper, the numerical simulation of the experimental setup is done with the FLUKA Monte Carlo radiation transport code. The calculated microdosimetric spectra are compared with the measured ones at different depths in tissue for a monoenergetic proton beam (E=62 MeV) and for a modulated SOBP. Numerically and experimentally predicted relative biological effectiveness values are in good agreement. The calculated frequency-averaged and dose-averaged lineal energy mean values are consistent with measured data.

The consideration of biological effectiveness of low energy protons using biophysical modeling of the effects induced by exposure of V79 cells

We have applied Monte Carlo track structure simulations to estimate relative biological effectiveness (RBE) of low-energy protons using biophysical modelling of radiation effects induced by exposure of V79 cells growing in mono-layer. The microscopic energy deposition in cell nucleus and sub-nucleus volumes was investigated in order to understand the reasons of enhanced biological effectiveness near Bragg peak. Theoretical estimations of RBE based on frequency/dose average lineal energy and calculated yields of initial DNA breaks were collated with experimental RBEM data. It was found: (1) dose average lineal energy for whole cell nucleus as a function of proton energy shows a distinct peak at 550 keV; (2) the peak values for subnucleus volumes are large compared with the whole cell nucleus; (3) the yield of complex DNA breaks correlates with experimental RBEM data.

Verification of biological dose calculation for carbon ion therapy with a monte carlo method.

We developed a calculation technique to evaluate the biological dose distribution of heavy ion beams, and verified its reliability by comparison with experimental results. The calculation technique was developed by connecting two general-purpose Monte Carlo codes. In order to evaluate the radiation quality and biological effect, the microdosimetric kinetic model was adopted. We estimated the distribution of physical dose and radiation quality for the carbon broad beam with experiments and with Monte Carlo calculations. Relative biological effectiveness (RBE) was estimated from radiation quality, and biological dose could be calculated as the product of the physical dose and the RBE. Our calculations showed good agreement with experiments, not only for the physical dose, but also for the dose-averaged lineal energy as an expression of radiation quality and therefore biological dose. This finding indicates that our calculation tool will be useful to estimate biological dose distribution in the design of heavy ion radiation facilities or for quality assurance in treatment planning.

Magnetic field effects on the energy deposition spectra of MV photon radiation

Several groups worldwide have proposed various concepts for improving megavoltage (MV) radiotherapy that involve irradiating patients in the presence of a magnetic field—either for image guidance in the case of hybrid radiotherapy-MRI machines or for purposes of introducing tighter control over dose distributions. The presence of a magnetic field alters the trajectory of charged particles between interactions with the medium and thus has the potential to alter energy deposition patterns within a sub-cellular target volume. In this work, we use the MC radiation transport code PENELOPE with appropriate algorithms invoked to incorporate magnetic field deflections to investigate electron energy fluence in the presence of a uniform magnetic field and the energy deposition spectra within a 10 µm water sphere as a function of magnetic field strength. The simulations suggest only very minor changes to the electron fluence even for extremely strong magnetic fields. Further, calculations of the dose-averaged lineal energy indicate that a magnetic field strength of at least 70 T is required before beam quality will change by more than 2%.

Modelling and calculations of the response of tissue equivalent proportional counter to charged particles

Space activities in earth orbit or in deep space pose challenges to the estimation of risk factors for both astronauts and instrumentation. In space, risk from exposure to ionising radiation is one of the main factors limiting manned space exploration. Therefore, characterising the radiation environment in terms of the types of radiations and the quantity of radiation that the astronauts are exposed to is of critical importance in planning space missions. In this paper, calculations of the response of TEPC to protons and carbon ions were reported. The calculations have been carried out using Monte Carlo track structure simulation codes for the walled and the wall-less TEPC counters. The model simulates nonhomogenous tracks in the sensitive volume of the counter and accounts for direct and indirect events. Calculated frequency- and dose-averaged lineal energies 0.3 MeV-1 GeV protons are presented and compared with the experimental data. The calculation of quality factors (QF) were made using individual track histories. Additionally, calculations of absolute frequencies of energy depositions in cylindrical targets, 100 nm height by 100 nm diameter, when randomly positioned and oriented in water irradiated with 1 Gy of protons of energy 0.3-100 MeV, is presented. The distributions show the clustering properties of protons of different energies in a 100 nm by 100 nm cylinder.

Comparisons of LET Distributions for Protons with Energies between 50 and 200 MeV Determined Using a Spherical Tissue-Equivalent Proportional Counter (TEPC) and a Position-Sensitive Silicon Spectrometer (RRMD-III)

Experiments have been performed to measure the response of a spherical tissue-equivalent proportional counter (TEPC) and a silicon-based LET spectrometer (RRMD-III) to protons with energies ranging from 50-200 MeV. This represents a large portion of the energy distribution for trapped protons encountered by astronauts in low-Earth orbit. The beam energies were obtained using plastic polycarbonate degraders with a monoenergetic beam that was extracted from a proton synchrotron. The LET spectrometer provided excellent agreement with the expected LET distribution emerging from the energy degraders. The TEPC cannot measure the LET distribution directly. However, the frequency mean value of lineal energy, y(-)(f), provided a good approximation to LET. This is in contrast to previous results for high-energy heavy ions where y(-)(f) underestimated LET, whereas the dose-averaged lineal energy, y(-)(D), provided a good approximation to LET.

Microdosimetric Analysis of Various Mammography Spectra: Lineal Energy Distributions and Ionization Cluster Analysis

In view of recent recommendations on the frequency and the starting age of mammography screening in healthy women, it is desirable to quantify the enhanced relative biological effectiveness (RBE) of mammography X rays compared to hard X rays. While there is little doubt that the former are more potent in inducing biological damage than the latter, the magnitude of the effect is still hotly debated in the literature. We used Monte Carlo simulations and track structure analysis in micrometer and nanometer volumes to investigate differences in distributions of lineal energy and ionization clusters for a range of mammography X-ray qualities. Dose-averaged lineal energies, (yD), in breast tissue for various mammography qualities were found to result in quality factors about 40% higher than unity. Among the various mammography qualities studied, the popular molybdenum/molybdenum target/filter combination was found to have the highest (yD) in 1-microm spheres (about 5.0 keV/microm near the entrance surface of breast tissue). In 10-nm radius spheres, the mean ionization cluster order was found to be about 35% higher in mammography X rays compared to 300 keV electrons (roughly representing 60Co or 192Ir photon radiation). In even smaller spheres (2 nm radius), no significant differences were observed for the mean ionization cluster order between mammography X rays and 300 keV electrons. We conclude that the potential of mammography X rays to induce biological damage is probably not much higher than a factor of two compared to hard X rays.

Theoretical analysis of microdosimetric spectra and cluster formation for 103Pd and 125I photon emitters**Presented at the WC 2003, 03.05B: Second International Workshop on Mini and Micro Dosimetry and Its Applications.

In this work we have compared 125I or 103Pd from a microdosimetric point of view. The photon spectra at different positions around the seeds have first been calculated using EGSnrc Monte Carlo (MC) code. These photon spectra are used as input for the event-by-event MC code TRION to calculate the microdosimetric lineal energy (y) distribution for each isotope. The microdosimetric dose average lineal energy, yD, calculated in a sphere of 1 µm is 3.5 keV µm−1 for 125I and 4.0 keV µm−1 for 103Pd, agreeing well with values reported in the literature. yD in a 1 µm sphere diminishes slightly with the distance from the seed for 103Pd. This is due to the spectral hardening caused by the presence of a gamma-ray of 357.5 keV in the initial spectrum of 103Pd. In parallel with the calculation of the microdosimetric spectra, we have analysed the distribution of the size of the energy deposition clusters generated by these low energy photons in structures of 2 and 10 nm of radius. Due to Compton interactions, the fraction of very low energy electrons (<5 keV) generated by 125I photons is 51%, whereas it is only 27% for 103Pd. As these electrons deposit their energy very locally, the pattern of energy depositions contains more clusters of a few nm of radius for 125I than for 103Pd; the mean cluster orders are respectively 3.3 and 3.0 for 10 nm clusters. This is in opposition with the prediction based on the microdosimetric spectrum and the parameter yD and could be of importance for the damage to the cells.