Dose-mean Lineal Energy Research Articles

LET-based approximation of the microdosimetric kinetic model for proton radiotherapy.

Phenomenological relative biological effectiveness (RBE) models for proton therapy, based on the dose-averaged linear energy transfer (LET), have been developed to address the apparent RBE increase towards the end of the proton range. The results of these phenomenological models substantially differ due to varying empirical assumptions and fitting functions. In contrast, more theory-based approaches are used in carbon ion radiotherapy, such as the microdosimetric kinetic model (MKM). However, implementing microdosimetry-based models in LET-based proton therapy treatment planning systems poses challenges. This work presents a LET-based version of the MKM that is practical for clinical use in proton radiotherapy. At first, we derived an approximation of the Mayo Clinic Florida (MCF) MKM for relatively-sparsely ionizing radiation such as protons. The mathematical formalism of the proposed model is equivalent to the original MKM, but it maintains some key features of the MCF MKM, such as the determination of model parameters from measurable cell characteristics. Subsequently, we carried out Monte Carlo calculations with PHITS in different simulated scenarios to establish a heuristic correlation between microdosimetric quantities and the dose averaged LET of protons. A simple allometric function was found able to describe the relationship between the dose-averaged LET of protons and the dose-mean lineal energy, which includes the contributions of secondary particles. The LET-based MKM was used to model the in vitro clonogenic survival RBE of five human and rodent cell lines (A549, AG01522, CHO, T98G, and U87) exposed to pristine and spread-out Bragg peak (SOBP) proton beams. The results of the LET-based MKM agree well with the biological data in a comparable or better way with respect to the other models included in the study. A sensitivity analysis on the model results was also performed. The LET-based MKM integrates the predictive theoretical framework of the MCF MKM with a straightforward mathematical description of the RBE based on the dose-averaged LET, a physical quantity readily available in modern treatment planning systems for proton therapy.

Lithium inelastic cross-sections and their impact on micro and nano dosimetry of boron neutron capture

Objective. To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV u−1. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques. Approach. The Classical Trajectory Monte Carlo method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV u−1 to 10 MeV u−1. Partial Li ion charge states ionization and excitation cross-sections were calculated using a detailed charge screening factor. The cross-sections were implemented in Geant4-DNA v10.07 and simulations and verified using TOPAS-nBio by calculating stopping power and continuous slowing down approximation (CSDA) range against data from ICRU and SRIM. Further microdosimetric and nanodosimetric calculations were performed to quantify differences against other simulation approaches for low energy Li ions. These calculations were: lineal energy spectra (yf(y) and yd(y)), frequency mean lineal energy yF― , dose mean lineal energy yD― and ionization cluster size distribution analysis. Microdosimetric calculations were compared against a previous MC study that neglected charge-exchange and excitation processes. Nanodosimetric results were compared against pure ionization scaled cross-sections calculations. Main results. Calculated stopping power differences between ICRU and Geant4-DNA decreased from 33.78% to 6.9%. The CSDA range difference decreased from 621% to 34% when compared against SRIM calculations. Geant4-DNA/TOPAS calculated dose mean lineal energy differed by 128% from the previous Monte Carlo. Ionization cluster size frequency distributions for Li ions differed by 76%–344.11% for 21 keV and 2 MeV respectively. With a decrease in the N 1 within 9% at 10 keV and agreeing after the 100 keV. With the new set of cross-sections being able to better simulate low energy behaviors of Li ions. Significance. This work shows an increase in detail gained from the use of a more complete set of low energy cross-sections which include charge exchange processes. Significant differences to previous simulation results were found at the microdosimetric and nanodosimetric scales that suggest that Li ions cause less ionizations per path length traveled but with more energy deposits. Microdosimetry results suggest that the BNC’s contribution to cellular death may be mainly due to alpha particle production when boron-based drugs are distributed in the cellular membrane and beyond and by Li when it is at the cell cytoplasm regions.

Low-pressure measurements of energy depositions in nanometre objects with a single ionisation chamber in a 60Co beam using the variance–covariance method

Dose-mean lineal energies were measured using the variance–covariance method and commercial ionisation chambers in a therapy level 60Co field at several different air pressures. The results confirmed the trend from previous studies and the experimental data was extended down to a simulated object diameter of 4.2 nm using a low-noise electrometer. The variance–covariance method was adapted to consecutive charge integrations from a single ionisation chamber and used to correct for signal variations due to pressure drifts in the ion chamber. Monte Carlo simulations using MCNP 6.2 were performed, and the results follow the trend of the experimental values in the nanometric region.

Microdosimetry at the nanometre level with different techniques

Microdosimetry provides the capability to measure probabilistic distributions of lineal energy in micrometer or sub-micrometer-sized volumes. The shape of these distributions is dependent on the size of the sensitive volume used for scoring, meant to approximate that of the relevant biological target. Recognizing that biological damage and its repair processes occur at different length scales, initiated by damages at the DNA level, single-event distributions can be measured with proportional counters in simulated sites as small as about 30 nm, but hardly below. However, direct measurement of dose-mean lineal energy can be achieved in even smaller site sizes, down to a few nm, using integrated current measurements with an ionization chamber and applying the variance-covariance technique. In this study, we investigate the agreement between dose-mean lineal energy values calculated from single-event distributions and those measured using the variance-covariance technique in photon radiation fields.

Sensitivity of a mini-TEPC to radiation quality variations in clinical proton beams

PurposeThis work aims at studying the sensitivity of a miniaturized Tissue-Equivalent Proportional Counter to variations of beam quality in clinical radiation fields, to further investigate its performances as radiation quality monitor. MethodsMeasurements were taken at the CATANA facility (INFN-LNS, Catania, Italy), in a monoenergetic and an energy-modulated proton beam with the same initial energy of 62 MeV. PMMA layers were placed in front of the detector to measure at different depths along the depth-dose profile. The frequency- and dose-mean lineal energy were compared to the track- and dose-averaged LET calculated by Monte Carlo simulations. A microdosimetric evaluation of the Relative Biological Effectiveness (RBE) was performed and compared with cell survival experiments. ResultsMicrodosimetric distributions measured at identical depths in the two beams show spectral differences reflecting their different radiation quality. Discrepancies are most evident at depths corresponding to the Spread-Out Bragg Peak, while spectra at the entrance and in the dose fall-off regions are similar. This can be explained by the different energy components that compose the pristine and spread-out peaks at each depth. The trend of microdosimetric mean values matches that of calculated LET averages along the entire penetration depth, and the microdosimetric estimation of RBE is consistent with radiobiological data not only at 2 Gy but also at lower dose levels, such as those absorbed by healthy tissues. ConclusionsThe mini-TEPC is sensitive to differences in radiation quality resulting from different modulations of the proton beam, confirming its potential for beam quality monitoring in proton therapy.

Secondary fragmentation and relative biological effectiveness (RBE) study using Bridge SOI microdosimeter: Monte Carlo simulation

Abstract Introduction: This work calculates the microdosimetric spectra and evaluates the relative biological effectiveness (RBE10) of oxygen and carbon ions using Monte Carlo simulation. This study presents a fast, reliable radiation field characterisation and accurate biological dose prediction tool in charged particle therapy for heavy-ion beams using the Bridge silicon-on-insulator (SOI) microdosimeter via Tool for Particle Simulation (TOPAS)-based simulations toolkit. Method: The study used the TOPAS simulation to model the Bridge SOI microdosimeter and study its response to carbon beams with an energy of 290 MeV/u and oxygen beams with an energy of 345 MeV/u. Dose-mean lineal energy values $(\overline {{y_D})\;} $ and RBE10 values were evaluated using microdosimetric lineal energy spectra with the MKM model. Results and Conclusions: The results demonstrate that oxygen ion beams have an advantage for cancer treatment as they provide higher RBE10 values and occur at the same positions as the maximum physical dose (Bragg peak), compared to carbon ion beams. The study provides new understanding of RBE for carbon and oxygen ions, as well as the relationship between physical doses and RBE.

Diamond based integrated detection system for dosimetric and microdosimetric characterization of radiotherapy ion beams.

Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high-spatial-resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron-doped CVD diamond. The cross-section of the sensitive volume of the dosimetric element is 4mm2 and 1μm-thick, while the microdosimetric one has an active cross-sectional area of 100×100μm2 and a thickness of about 6.2μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7MeV/u and proton beam of 148.7MeV. The particle flux in the region of the microdosimeter was 6·107 cm2 /s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE-Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd ), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation.

GPU-accelerated calculation of proton microdosimetric spectra as a function of target size, proton energy, and bounding volume size

Objective. Shortcomings of dose-averaged linear energy transfer (LETD), the quantity which is most commonly used to quantify proton relative biological effectiveness, have long been recognized. Microdosimetric spectra may overcome the limitations of LETD but are extremely computationally demanding to calculate. A systematic library of lineal energy spectra for monoenergetic protons could enable rapid determination of microdosimetric spectra in a clinical environment. The objective of this work was to calculate and validate such a library of lineal energy spectra. Approach. SuperTrack, a GPU-accelerated CUDA/C++ based application, was developed to superimpose tracks calculated using Geant4 onto targets of interest and to compute microdosimetric spectra. Lineal energy spectra of protons with energies from 0.1 to 100 MeV were determined in spherical targets of diameters from 1 nm to 10 μm and in bounding voxels with side lengths of 5 μm and 3 mm. Main results. Compared to an analogous Geant4-based application, SuperTrack is up to 3500 times more computationally efficient if each track is resampled 1000 times. Dose spectra of lineal energy and dose-mean lineal energy calculated with SuperTrack were consistent with values published in the literature and with comparison to a Geant4 simulation. Using SuperTrack, we developed the largest known library of proton microdosimetric spectra as a function of primary proton energy, target size, and bounding volume size. Significance. SuperTrack greatly increases the computational efficiency of the calculation of microdosimetric spectra. The elevated lineal energy observed in a 3 mm side length bounding volume suggests that lineal energy spectra determined experimentally or computed in small bounding volumes may not be representative of the lineal energy spectra in voxels of a dose calculation grid. The library of lineal energy spectra calculated in this work could be integrated with a treatment planning system for rapid determination of lineal energy spectra in patient geometries.

Microdosimetry with a mini-TEPC in the spread-out Bragg peak of 148 MeV protons

A new miniaturized Tissue Equivalent Proportional Counter (mini‒TEPC) with cylindrical sensitive volume of 1.0 mm in diameter and height, and with external diameter of 1.53 cm, has been developed to work without gas flow. With this mini counter we have measured the radiation quality of the 148 MeV energy-modulated proton beam at the radiobiological research line of the Trento Proton Therapy Centre. The irradiation field had a diameter of about 6 cm, a modulation width of 2.5 cm and a range of about 13.5 cm. At four specific depths, the response function of the new microdosimeter has also been compared to that of a commercial spherical microdosimeter, the LET-1/2” Spherical TEPC produced by Far West Technology. Afterwards, measurements were performed with the mini‒TEPC at nine precise positions across the Spread-Out Bragg Peak (SOBP).From the microdosimetric spectra the frequency and the dose‒mean lineal energy values, y‾F and y‾D, were derived for both detectors. Afterwards, microdosimetric assessment of Relative Biological Effectiveness (RBEμ) has been performed by weighting the dose distribution of the lineal energy, d(y), with the Loncol’s biological weighting function r(y).RBEμ has been used to calculate the RBEμD at different dose levels D. In the distal fall-off region the RBEμD(d) increases significantly, up to a factor 3. Finally, the RBEμD-weighted dose was calculated and compared to that obtained with a fixed RBE = 1.1. The use of a variable RBE to weight the physical dose leads to a biological range extension evaluated at R80 of about 2.0 mm, with respect to the R80 obtained with a fixed RBE = 1.1.The use of a mini‒TEPC in proton therapy has been so far limited to 60 MeV proton beams, used for the treatment of ocular melanoma. This is the first time that a mini-TEPC was used with an higher energy proton beam of 148 MeV, and the spectra measured with the mini-TEPC were compared to those measured with the commercial FWT LET1/2 counter for the first time.These new results corroborate the usability of mini-TEPCs in proton therapy.

On the measurement uncertainty of microdosimetric quantities using diamond and silicon microdosimeters in carbon-ion beams.

The purpose of this paper is to compare the response of two different types of solid-state microdosimeters, that is, silicon and diamond, and their uncertainties. A study of the conversion of silicon microdosimetric spectra to the diamond equivalent for microdosimeters with different geometry of the sensitive volumes is performed, including the use of different stopping power databases. Diamond and silicon microdosimeters were irradiated under the same conditions, aligned at the same depth in a carbon-ion beam at the MedAustron ion therapy center. In order to estimate the microdosimetric quantities, the readout electronic linearity was investigated with three different methods, that is, the first being a single linear regression, the second consisting of a double linear regression with a channel transition and last a multiple linear regression by splitting the data into odd and even groups. The uncertainty related to each of these methods was estimated as well. The edge calibration was performed using the intercept with the horizontal axis of the tangent through the inflection point of the Fermi function approximation multi-channel analyzer spectrum. It was assumed that this point corresponds to the maximum energy difference of particle traversing the sensitive volume (SV) for which the residual range difference in the continuous slowing down approximation is equal to the thickness of the SV of the microdosimeter. Four material conversion methods were explored, the edge method, the density method, the maximum-deposition energy method and the bin-by-bin transformation method. The uncertainties of the microdosimetric quantities resulting from the linearization, the edge calibration and the detectors thickness were also estimated. It was found that the double linear regression had the lowest uncertainty for both microdosimeters. The propagated standard (k = 1) uncertainties on the frequency-mean lineal energy and the dose-mean lineal energy values from the marker point, in the spectra, in the plateau were 0.1% and 0.2%, respectively, for the diamond microdosimeter, whilst for the silicon microdosimeter data converted to diamond, the uncertainty was estimated to be 0.1%. In the range corresponding to the 90% of the amplitude of the Bragg Peak at the distal part of the Bragg curve (R90 ) the uncertainty was found to be 0.1%. The uncertainty propagation from the stopping power tables was estimated to be between 5% and 7% depending on the method. The uncertainty on the and coming from the thickness of the detectors varied between 0.3% and 0.5%. This article demonstrate that the linearity of the readout electronics affects the microdosimetric spectra with a difference in values between the different linearization methods of up to 17.5%. The combined uncertainty was dominated by the uncertainty of stopping power on the edge.

Experimental and Monte Carlo based study of different microdosimetric quantities at mixed radiation environments of nuclear reactor, reprocessing facility and D-D accelerator

Personnel working in the environment of nuclear reactors, fuel reprocessing facilities, high energy accelerators get exposed to a mixed radiation field of electrons, photons, and neutrons with a wide range of energy and fluence. Performance evaluations of the passive personnel dosimeters in these mixed radiation environments require knowledge of the external dose contributed by different types of radiations having variation in their energy, etc. Tissue Equivalent Proportional Counters (TEPC), sensitive to a wide range of particles and energy (Linear Energy Transfer (LET) ∼ 0–1500 keV μm−1), is one of the standard reference detectors which can be used for the characterization of mixed radiation fields. In the present work, HAWK TEPC was used to evaluate different microdosimetric parameters such as dose mean lineal energy (ӯD), average quality factor (Ǭ), the contribution of gamma and neutron dose equivalents for the characterizations of the radiation fields inside in a nuclear research reactor hall, fuel reprocessing facility, D-D neutron beam facility, radionuclide source based neutron calibration facilities, etc. Measured results were compared with Monte Carlo simulated values using radiation transport code PHITS. TEPC measurement shows that the radiation work field around nuclear reactor facility is dominated by gamma rays with approximate ӯD and Ǭ of ∼42 keV μm−1 and ∼2.3, respectively. Whereas ӯD and Ǭ values for neutron dominated locations in fuel reprocessing facility are 82 keV μm−1 and 8.2, respectively. Ǭ values near thermal neutron beam line in research reactor are close to 1 due to (n, γ) reaction. For 2.54 MeV mono-energetic D-D neutron beam, measured and calculated dose mean lineal energies (ӯD) are 52.5 keV μm−1 and 59.6 keV μm−1, respectively, whereas corresponding Ǭ values are 11.23 and 13.01. Obtained values can be utilized to correlate the neutron and gamma dose equivalents measured by passive detectors used for personnel monitoring program to enhance confidence in the dosimetry.

Range-shifter effects on the stray field in proton therapy measured with the variance-covariance method.

Measurements in the stray radiation field from a proton therapy pencil beam at energies 70 and 146 MeV were performed using microdosimetric tissue-equivalent proportional counters (TEPCs). The detector volumes were filled with a propane-based tissue-equivalent gas at low pressure simulating a mean chord length of 2 μm in tissue. Investigations were performed with and without a beam range shifter, and with different air gaps between the range shifter and a solid water phantom. The absorbed dose, the dose-mean lineal energy, and the dose equivalent were determined for different detector positions using the variance–covariance method. The influence from beam energy, detector- and range-shifter positions on absorbed dose, LET, and dose equivalent were investigated. Monte Carlo simulations of the fluence, detector response, and absorbed dose contribution from different particles were performed with MCNP 6.2. The simulated dose response for protons, neutrons, and photons were compared with, and showed good agreement with, previously published experimental data. The simulations also showed that the TEPC absorbed dose agrees well with the ambient absorbed dose for neutron energies above 20 MeV. The results illustrate that changes in both dose and LET variations in the stray radiation field can be identified from TEPC measurements using the variance–covariance method. The results are in line with the changes seen in the simulated relative dose contributions from different particles associated with different proton energies and range-shifter settings. It is shown that the proton contribution scattered directly from the range shifter dominates in some situations, and although the LET of the radiation is decreased, the ambient dose equivalent is increased up to a factor of 3.

A systematic study of the contribution of counting statistics to the final lineal energy uncertainty in microdosimetry

Objectives. Microdosimetry is proving to be a reliable and powerful tool to be applied in different fields such as radiobiology, radiation protection and hadron therapy. However, accepted standard protocols and codes of practice are still missing. With this regard, a systematic and methodical uncertainty analysis is fundamental to build an accredited uncertainty budget of practical use. This work studied the contribution of counting statistics (i.e. number of events collected) to the final frequency-mean and dose-mean lineal energy uncertainties, aiming at providing guidelines for good experimental and simulation practice. The practical limitation of current technologies and the non-negligible probability of nuclear reactions require careful considerations and nonlinear approaches. Approach. Microdosimetric data were obtained by means of the particle tracking Monte Carlo code Geant4. The uncertainty analysis was carried out relying on a Monte Carlo based numerical analysis, as suggested by the BIPM's ‘Guide to the expression of uncertainty in measurement’. Final uncertainties were systematically investigated for proton, helium and carbon ions at an increasing number of detected events, for a range of different clinical-relevant beam energies. Main results. Rare events generated by nuclear interactions in the detector sensitive volume were found to massively degrade microdosimetric uncertainties unless a very high statistics is collected. The study showed an increasing impact of such events for increasing beam energy and lighter ions. For instance, in the entrance region of a 250 MeV proton beam, about 5 ∗ 107 events need to be collected to obtain a dose-mean lineal energy uncertainty below 10%. Significance. The results of this study help define the necessary conditions to achieve appropriate statistics in computational microdosimetry, pointing out the importance of properly taking into account nuclear interaction events. Their impact on microdosimetric quantities and on their uncertainty is significant and cannot be overlooked, particularly when characterising clinical beams and radiobiological response. This work prepared the ground for deeper investigations involving dedicated experiments and for the development of a method to properly evaluate the counting statistics uncertainty contribution in the uncertainty budget, whose accuracy is fundamental for the clinical transition of microdosimetry.

Predicting the Biological Effects of Human Salivary Gland Tumour Cells for Scanned 4He-, 12C-, 16O-, and 20Ne-Ion Beams Using an SOI Microdosimeter

Experimental microdosimetry along with the microdosimetric kinetic (MK) model can be utilized to predict the biological effects of ions. To predict the relative biological effectiveness (RBE) of ions and the survival fraction (SF) of human salivary gland tumour (HSGc-C5) cells, microdosimetric quantities measured by a silicon-on-insulator (SOI) MicroPlus-mushroom microdosimeter along the spread-out Bragg peak (SOBP) delivered by pencil beam scanning of 4He, 12C, 16O, and 20Ne ions were used. The MK model parameters of HSGc-C5 cells were obtained from the best fit of the calculated SF for the different linear energy transfer (LET) of these ions and the formerly reported in vitro SF for the same LET and ions used for calculations. For a cube-shaped target of 10 × 10 × 6 cm3, treatment plans for 4He, 12C, 16O, and 20Ne ions were produced with proprietary treatment planning software (TPS) aiming for 10% SF of HSGc-C5 cells over the target volume and were delivered to a polymethyl methacrylate (PMMA) phantom. Afterwards, the saturation-corrected dose-mean lineal energy derived based on the measured microdosimetry spectra, along with the physical dose at various depths in PMMA phantoms, was used for the estimation of the SF, RBE, and RBE-weighted dose using the MK model. The predicted SF, RBE, and the RBE-weighted dose agreed with what was planned by the TPS within 3% at most depths for these ions.

DNA strand breaks based on Monte Carlo simulation in and around the Lipiodol with flattening filter and flattening filter-free photon beams.

BackgroundThe current study aims to investigate the DNA strand breaks based on the Monte Carlo simulation within and around the Lipiodol with flattening filter (FF) and flattening filter-free (FFF) photon beams.Materials and methodsThe dose-mean lineal energy (yD) and DNA single- and double strand breaks (DSB/SSB) based on spatial patterns of inelastic interactions were calculated using the Monte Carlo code: particle and heavy ion transport system (PHITS). The ratios of dose using standard radiation (200 kVX) to the dose of test radiation (FF and FFF of 6 MV X-ray (6MVX) and 10 MVX beams) to produce the same biological effects was defined as RBEDSB. The RBEDSB within the Lipiodol and in the build-up and build-down regions was evaluated.ResultsThe RBEDSB values with the Lipiodol was larger than that without the Lipiodol at the depth of 4.9 cm by 4.2% and 2.5% for 6 MVX FFF and FF beams, and 3.3% and 2.5% for 10 MVX FFF and FF beams. The RBEDSB values with the Lipiodol was larger than that without the Lipiodol at the depth of 6.5 cm by 2.9% and 2.4% for 6 MVX FFF and FF beams, and 1.9% and 1.4% for 10 MVX FFF and FF beams. In the build-down region at the depth of 8.1 cm, the RBEDSB values with the Lipiodol was smaller than that without the Lipiodol by 4.2% and 2.9% for 6 MVX FFF and FF beams, and 1.4% and 0.1% for 10 MVX FFF and FF beams.ConclusionsThe current study simulated the DNA strand break except for the physical dose difference. The lower and FFF beam occurred the higher biological effect.

The Occurred Error in Microdosimetry Calculations while using Water Instead of the Body Organs in Proton Therapy and a New Formula for an Estimate of the Statistical Uncertainty of Microdosimetric Quantities

In many experimental and simulation researches, water phantom is used instead of most body organs. Therefore, in this study, we replaced the water phantom instead of some organs to calculate its effect on the proton stopping-power, and range and the consequence of deposited energy and microdosimetric spectra in small sites. Some organs such as the spleen, thyroid, pancreas, prostate, testis, and ovaries are considered. We calculated the proton stopping-power in these organs using the SRIM code. Then using these results, we wrote a program in the programming language of Fortran and computed the proton range and deposited energy in two sites of 1 and 100 micron. Also, using the Geant4-10-4 code, we simulated these sites and obtained microdosimetric spectra of protons at 1 and 5MeV energies. In order to compare different states, the frequency-mean lineal energy, dose-mean lineal energy, these statistical uncertainties and absorb dose in each case were calculated and reported. Also, we estimated the statistical uncertainty of quantities with a new formula. We observed that using water instead of the organs causes a significant error in the calculations of the range and the maximum relative difference percentage of 18% and 22% in deposited energy in 1 and 100 micron sites, respectively. These differences depend on the energy of the incident proton, organ, and size site. Also, this replacement changes microdosimetric spectra, the location, and intensity of the Bragg's peak. The percent difference of location and intensity of the Bragg's peak for water instead of the spleen is -8.66 and 13.42%, respectively. Therefore, using water instead of the body organs in microdosimetry calculations is not recommended.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector

Objective. Treatment planning based on computer simulations was proposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach. Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 μm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose-mean values, and the RBE calculated with a biological weighting function were compared with PHITS simulations (microdosimetric target = 1 μm water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results. Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose-mean lineal energy and the RBE10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance. This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

Dose‐mean lineal energy values for electrons by different Monte Carlo codes: Consequences for estimates of radiation quality in photon beams

The microdosimetric quantity lineal energy and its mean values have proven useful for quantifying radiation quality in many situations. The ratio of dose-mean lineal energies is perhaps the simplest quantity for quantifying differences between two radiation qualities. However, published dose-mean lineal energy values from different codes may differ significantly with potential influence on radiation quality estimates. The purpose was to compare dose-mean lineal energy values from different track-structure data sets for condensed water vapor and liquid water, and to evaluate the influence on radiation quality estimations for some photon sources. Published dose-mean lineal energy values for 0.1keV to 1 MeV electrons in spheres with diameters 2nm to 1μm, calculated with water vapor and liquid water track structure codes and proximity functions, were collected, analyzed, and compared. Data for cylinders were converted to spheres using a theoretical transformation published by Kellerer. A new set of dose-mean lineal energy values was calculated to cover the whole range of volumes of interest here using the GEANT4-DNA code. The influence from the differences between codes on radiation quality calculations was estimated using dose-mean lineal energy ratios for the photon sources 125 I, 169 Yb, and 192 Ir relative to 60 Co. The theoretical relation for converting the dose-mean lineal energy between different geometrical volumes, results in differences up to 10% between cylinders and spheres depending on electron energy and target size, in agreement with published simulated results. For spheres with diameter above 100nm, dose-mean lineal energy values for condensed water vapor and liquid water are with few exceptions within ±10%. Below 100nm, the difference increases with decreasing diameter reaching a factor of two at 2nm. The values from water vapor codes are in general larger than from liquid water codes. If the dose-mean lineal energy ratio is based on condensed water vapor instead of liquid water, the ratio differs less than 9% for the nuclides 125 I, 169 Yb, and 192 Ir relative to 60 Co independent of the volume simulated. However, a specific value of the dose-mean lineal energy ratio, is found at a larger target diameter in liquid water than in condensed water vapor. When ratios of the dose-mean lineal energy are used as a measure of the radiation quality it is important to compare values for geometrically equal target shapes. A practical method of converting values for cylinders of equal diameter and height to spheres was demonstrated. Although dose-mean lineal energy values calculated with water vapor and liquid water codes may differ significantly, the radiation quality, in terms of ratios of dose-mean lineal energy, for the three photon sources 192 Ir, 169 Yb, and 125 I relative to 60 Co, agree within 9%. The same ratio appears at a larger diameter when a liquid water code is used. It is therefore important to use the same code in radiation quality investigations. The present findings may be of special interest in studies related to the relative biological effectiveness (RBE).

The relation between microdosimetry and induction of direct damage to DNA by alpha particles

In radiopharmaceutical treatments α-particles are employed to treat tumor cells. However, the mechanism that drives the biological effect induced is not well known. Being ionizing radiation, α-particles can affect biological organisms by producing damage to the DNA, either directly or indirectly. Following the principle that microdosimetry theory accounts for the stochastic way in which radiation deposits energy in sub-cellular sized volumes via physical collisions, we postulate that microdosimetry represents a reasonable framework to characterize the statistical nature of direct damage induction by α-particles to DNA. We used the TOPAS-nBio Monte Carlo package to simulate direct damage produced by monoenergetic alpha particles to different DNA structures. In separate simulations, we obtained the frequency-mean lineal energy () and dose-mean lineal energy () of microdosimetric distributions sampled with spherical sites of different sizes. The total number of DNA strand breaks, double strand breaks (DSBs) and complex strand breaks per track were quantified and presented as a function of either or The probability of interaction between a track and the DNA depends on how the base pairs are compacted. To characterize this variability on compactness, spherical sites of different size were used to match these probabilities of interaction, correlating the size-dependent specific energy () with the damage induced. The total number of DNA strand breaks per track was found to linearly correlate with and when using what we defined an effective volume as microdosimetric site, while the yield of DSB per unit dose linearly correlated with or being larger for compacted than for unfolded DNA structures. The yield of complex breaks per unit dose exhibited a quadratic behavior with respect to and a greater difference among DNA compactness levels. Microdosimetric quantities correlate with the direct damage imparted on DNA.

Uncertainty in tissue equivalent proportional counter assessments of microdosimetry and RBE estimates in carbon radiotherapy

Microdosimetry is an important tool for assessing energy deposition distributions from ionizing radiation at cellular and cellular nucleus scales. It has served as an input parameter for multiple common mathematical models, including evaluation of relative biological effectiveness (RBE) of carbon ion therapy. The most common detector used for microdosimetry is the tissue-equivalent proportional counter (TEPC). Although it is widely applied, TEPC has various inherent uncertainties. Therefore, this work quantified the magnitude of TEPC measurement uncertainties and their impact on RBE estimates for therapeutic carbon beams. Microdosimetric spectra and frequency-, dose-, and saturation-corrected dose-mean lineal energy (****) were calculated using the Monte Carlo toolkit Geant4 for five monoenergetic and three spread-out Bragg peak carbon beams in water at every millimeter along the central beam axis. We simulated the following influences on these spectra from eight sources of uncertainty: wall effects, pulse pile-up, electronics, gas pressure, W-value, gain instability, low energy cut-off, and counting statistics. Statistic uncertainty was quantified as the standard deviation of perturbed values for each source. Bias was quantified as the difference between default lineal energy values and the mean of perturbed values for each systematic source. Uncertainties were propagated to RBE using the modified microdosimetric kinetic model (MKM). Variance introduced by statistic sources in and averaged 3.8% and 3.4%, respectively, and 1.5% in across beam depths and energies. Bias averaged 6.2% and 7.3% in and and 4.8% in These uncertainties corresponded to 1.2 ± 0.9% on average in RBEMKM. The largest contributors to variance and bias were pulse pile-up and wall effects. This study established an error budget for microdosimetric carbon measurements by quantifying uncertainty inherent to TEPC measurements. It is necessary to understand how robust the measurement of RBE model input parameters are against this uncertainty in order to verify clinical model implementation.