Microdosimetric Distributions Research Articles

Comparative Evaluation of Two Analytical Functions for the Microdosimetry of Ions from 1H to 238U

The analytical microdosimetric function (AMF) implemented in the Monte Carlo code PHITS is a unique tool that bridges the gap between macro- and microscopic scales of radiation interactions, enabling accurate microdosimetric calculations over macroscopic bodies. The original AMF was published in 2006, based on the results of track structure calculations. Recently, a newer version of the AMF was proposed, incorporating an improved description of the energy loss at the microscopic scale. This study compares the older and the newer AMFs in computing microdosimetric probability distributions, mean values, and the relative biological effectiveness (RBE). To this end, 16,000 microdosimetric lineal energy probability density distributions were simulated with PHITS for ions from 1H to 238U over a broad energy range (1–1000 MeV/n). The newer AMF was found to offer superior performance, particularly for very heavy ions, producing results that align more closely with published in vitro clonogenic survival experiments. These findings suggest that the updated AMF provides a more reliable tool for microdosimetric calculations and RBE modeling, essential for ion radiation therapy and space radiation protection.

Calculation of biological effectiveness of SOBP proton beams: a TOPAS Monte Carlo study

Objective. This study aims to investigate the biological effectiveness of Spread-Out Bragg-Peak (SOBP) proton beams with initial kinetic energies 50–250 MeV at different depths in water using TOPAS Monte Carlo code. Approach. The study modelled SOBP proton beams using TOPAS time feature. Various LET-based models and Repair-Misrepair-Fixation model were employed to calculate Relative Biological Effectiveness (RBE) for V79 cell lines at different on-axis depths based on TOPAS. Microdosimetric Kinetic Model and biological weighting function-based models, which utilize microdosimetric distributions, were also used to estimate the RBE. A phase-space-based method was adopted for calculating microdosimetric distributions. Main results. The trend of variation of RBE with depth is similar in all the RBE models, but the absolute RBE values vary based on the calculation models. RBE sharply increases at the distal edge of SOBP proton beams. In the entrance region of all the proton beams, RBE values at 4 Gy i.e. RBE(4 Gy) resulting from different models are in the range of 1.04–1.07, comparable to clinically used generic RBE of 1.1. Moving from the proximal to distal end of the SOBP, RBE(4 Gy) is in the range of 1.15–1.33, 1.13–1.21, 1.11–1.17, 1.13–1.18 and 1.17–1.21, respectively for 50, 100, 150, 200 and 250 MeV SOBP beams, whereas at the distal dose fall-off region, these values are 1.68, 1.53, 1.44, 1.42 and 1.40, respectively. Significance. The study emphasises application of depth-, dose- and energy- dependent RBE values in clinical application of proton beams.

Integrating microdosimetricin vitroRBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeliNg for RBE ASsessment (MONAS) tool.

Objective.In this paper, we present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE.Approach.MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers to calculate the single- and multi-event specific energy microdosimetric distributions at different micrometer scales. These spectra are used as physical input to three different formulations of themicrodosimetric kinetic model, and to thegeneralized stochastic microdosimetric model(GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra andin vitrosurvival fraction data. To show the MONAS features, we present two different applications of the code: (i) the depth-RBE curve calculation from a passively scattered proton SOBP and monoenergetic12C-ion beam by using experimentally validated spectra as physical input, and (ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons.Main results.MONAS can estimate dose-dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP and12C fields, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target.Significance.MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, pushing closer the experimental physics-based description to the biological damage assessment, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE.

Microdosimetry-based investigation of biological effectiveness of 252Cf brachytherapy source: TOPAS Monte Carlo study

Objective. To investigate biological effectiveness of 252Cf brachytherapy source using Monte Carlo-calculated microdosimetric distributions. Approach. 252Cf source capsule was placed at the center of the spherical water phantom and phase-space data were scored as a function of radial distance in water (R = 1–5 cm) using TOPAS Monte Carlo code. The phase-space data were used to calculate microdosimetric distributions at 1 μm site size. Using these distributions, Relative Biological Effectiveness (RBE), mean quality factor () and Oxygen Enhancement Ratio (OER) were calculated as a function of R. Main results. The overall shapes of the microdosimetric distributions are comparable at all the radial distances in water. However, slight variation in the bin-wise yield is observed with R. RBE, and OER are insensitive to R over the range 1–5 cm. Microdosimetric kinetic model based RBE values are about 2.3 and 2.8 for HSG tumour cells and V79 cells, respectively, whereas biological weighting function-based RBE is about 2.8. ICRP 60 and ICRU 40 recommendation-based values are about 14.5 and 16, respectively. Theory of dual radiation action based RBE is 11.4. The calculated value of OER is 1.6. Significance. This study demonstrates the relative insensitivity of RBE, and OER radially away from the 252Cf source along the distances of 1–5 cm in water.

Investigation of the anisotropic distribution of microdosimetric quantities in the vicinity of X-ray-irradiated gold nanoparticles

High-Z nanoparticles incorporated in tumors have great potential to enhance radiotherapy treatments by increasing the absorbed radiation dose in the vicinity of the nanoparticle. However, current Monte Carlo simulations estimate dose enhancement metrics in 1D, neglecting the anisotropy of the energy deposition around the nanoparticle. This could have radiobiological consequences and affect treatment accuracy. Accurate knowledge of the spatial distribution of the dose or other microdosimetric quantities is necessary for predicting radiobiological outcomes using biophysical models. In this study, we utilized a new combination of two Monte Carlo Variance Reduction Techniques (VRTs) to estimate microdosimetric quantities at the nanoscale, taking into account the anisotropy of the microdosimetric distributions. Our results show significant anisotropy in multi-events frequency-mean specific energy, as well as in microdosimetric distributions. These findings highlight the importance of considering anisotropy in microdosimetric distributions when predicting radiobiological outcomes and suggest that current 1D simulations may not accurately represent the real microdosimetric effects. Our work contributes to the development of multiscale dosimetry approaches for radiotherapy treatments with high-Z nanoparticles.

Microdosimetric assessment about proton spread-out Bragg peak at different depths based on the normal human mesh-type cell population model.

Objective.In clinical proton therapy, the spread-out Bragg peak (SOBP) is commonly used to fit the target shape. Dose depositions at microscopic sites vary, even with a consistent absorbed dose (D) in SOBP. In the present study, monolayer mesh-type cell population models were developed for microdosimetric assessment at different SOBP depths.Approach.Normal human bronchial epithelial (BEAS-2B) and hepatocytes (L-O2) mesh-type cell models were constructed based on fluorescence tomography images of normal human cells. Particle transport simulation in cell populations was performed coupled with Monte Carlo software PHITS. The relationship between microdosimetry and macrodosimetry of SOBP at different depths was described by analyzing the microdosimetric indicators such as specific energyz,specific energy distributionfz,D,and relative standard deviationσz/z¯within cells. Additionally, the microdosimetric distributions characteristics and their contributing factors were also discussed.Main results.The microscopic dose distribution is strongly influenced by cellular size, shape, and material. The mean specific energyz¯of nucleus and cytoplasm in the cell population is greater than the overall absorbed dose of the cell population model (Dp), with a maximumz¯/Dpof 1.1. The cellular dose distribution is different between the BEAS-2B mesh-type model and its concentric ellipsoid geometry-type model, which difference inz¯is about 10.3% for the nucleus and about 7.5% for the cytoplasm with the SOBP depth of 15 cm. WhenD= 2 Gy, the maximumzof L-O2 nucleus reaches 2.8 Gy andσz/z¯is 5.1% at the mid-depth SOBP (16-18 cm); while the maximumzof the BEAS-2B nucleus reaches 2.2 Gy with only 2.7% ofσz/z¯.Significance.The significant variation of microdosimetric distributions of SOBP different depths indicates the necessity to use mesh-type cell population models, which have the potential to be compared with biological results and build the bio-physical model.

A methodology to abridge microdosimetric distributions without a significant loss of the spectral information needed for the RBE computation in carbon ion therapy.

In order to compute the relative biological effectiveness (RBE) of ion radiation therapy with the Mayo Clinic Florida microdosimetric kinetic model (MCF MKM), it is necessary to process entire microdosimetric distributions. Therefore, a posteriori RBE recalculations (i.e., for a different cell line or another biological endpoint) would require whole spectral information. It is currently not practical to compute and store all this data for each clinical voxel. To develop a methodology that allows to store a limited amount of physical information without losing accuracy in the RBE calculations nor the possibility of a posteriori RBE recalculations. Computer simulations for four monoenergetic 12 C ion beams and a 12 C ion spread-out Bragg peak (SOBP) were performed to assess lineal energy distributions as a function of the depth within a water phantom. These distributions were used in combination with the MCF MKM to compute the in vitro clonogenic survival RBE for human salivary gland tumor cells (HSG cell line) and human skin fibroblasts (NB1RGB cell line). The RBE values were also calculated with a new abridged microdosimetric distribution methodology (AMDM) and compared with the reference RBE calculations using the entire distributions. The maximum relative deviation between the RBE values computed using the entire distributions and the AMDM was 0.61% (monoenergetic beams) and 0.49% (SOBP) for the HSG cell line, while 0.45% (monoenergetic beams) and 0.26% (SOBP) for the NB1RGB cell line. The excellent agreement between the RBE values computed using the entire lineal energy distributions and the AMDM represents a milestone for the clinical implementation of the MCF MKM.

MINAS TIRITH: a new tool for simulating radiation-induced DNA damage at the cell population level

Objective. The mechanisms of radiation-induced DNA damage can be understood via the fundamental acquisition of knowledge through a combination of experiments and modeling. Currently, most biological experiments are performed by irradiating an entire cell population, whereas modeling of radiation-induced effects is usually performed via Monte Carlo simulations with track structure codes coupled to realistic DNA geometries of a single-cell nucleus. However, the difference in scale between the two methods hinders a direct comparison because the dose distribution in the cell population is not necessarily uniform owing to the stochastic nature of the energy deposition. Thus, this study proposed the MINAS TIRITH tool to model the distribution of radiation-induced DNA damage in a cell population. Approach. The proposed method is based on precomputed databases of microdosimetric parameters and DNA damage distributions generated using the Geant4-DNA Monte Carlo Toolkit. First, a specific energy was assigned to each cell of an irradiated population for a particular absorbed dose following microdosimetric formalism. Then, each cell was assigned a realistic number of DNA damage events according to the specific energy respecting the stochastic character of its occurrence. Main results. This study validated the MINAS TIRITH tool by comparing its results with those obtained using the Geant4-DNA track structure code and a Geant4-DNA based simulation chain for DNA damage calculation. The different elements of comparison indicated consistency between MINAS TIRITH and the Monte Carlo simulation in case of the dose distribution in the population and the calculation of the amount of DNA damage. Significance. MINAS TIRITH is a new approach for the calculation of radiation-induced DNA damage at the cell population level that facilitates reasonable simulation times compared to those obtained with track structure codes. Moreover, this tool enables a more direct comparison between modeling and biological experimentation.

Microdosimetry-based quality factors for ISO reference photon and beta sources: TOPAS Monte Carlo study

In radiological protection, personnel dosimeters are calibrated in terms of operational quantities such as H p (10) and H p (0.07) against ISO reference photon and beta sources, respectively. H p (10) and H p (0.07) are defined at 1 cm and 0.07 μm depths in the ICRU-4 element tissue phantom. In present study, mean quality factor Q̅ is calculated at these depths using the TOPAS-based microdosimetric distributions at 1 μm site size and FLUKA-based Linear Energy Transfer (LET) dependent Q̅. The sources simulated are ISO reference narrow series X-rays, 137Cs and 147Pm, 85Kr, 90Sr/90Y and 106Ru/106Rh beta sources. Using the calculated microdosimetric distributions, Q̅ is calculated based on ICRP60 and ICRU40 recommendations, Keller-Hahn (KH) approximation, Microdosimetric Kinetic Model (MKM), Clonogenic Survival and Theory of Dual Radiation Action (TDRA). The study includes FLUKA-based Q̅ values calculated using Q(L) vs L relationship as per ICRP Report 60. The MKM, Clonogenic Survival-based RBE, ICRU40, TDRA and KH-based Q values of all the investigated sources are about unity. Depending on the source, microdosimetry-based Q̅ values using ICRP60 recommendations show significant difference from that calculated using other models. Q̅ values of 137Cs are unity, independent of the models.

Comparison of 126 MeV antiproton and proton—a FLUKA-based microdosimetric approach

Objective. This study aims at comparing dosimetric parameters of 126 MeV antiprotons and protons using microdosimetric approach. Approach. Microdosimetric distributions of 126 MeV proton and antiproton beams at 1 μm site size are calculated using the Monte Carlo-based FLUKA code. The distributions are calculated at various depths along the central axis in water phantom as well as at different off-axis locations. The study also includes calculations of secondary radiations produced by antiprotons and protons. Mean quality factor, is calculated using the ICRP 60 and ICRU 40 recommendations. The Relative Biological Effectiveness (RBE) of HSG tumour cell at 10% survival level is calculated based on Microdosimetric Kinetic Model. Main results. and RBE for antiprotons are higher by a factor of about 3.60, 3.41 and 1.24, respectively, at Bragg-peak and higher by a factor of about 1.41, 1.76 and 1.05, respectively, at plateau region of depth-dose profile when compared to protons. At 15 cm depth along the central axis, and RBE for protons are higher by a factor of about 1.42, 1.66 and 1.26, respectively, when compared to antiprotons. At the off-axis distance (Ld ) of 6 cm (at 11.5 cm depth in water), and of protons are higher than that of antiproton whereas the trend is opposite at off-axis distance of 4 cm. At Ld = 4 cm (at 11.5 cm depth in water), RBE of antiprotons is higher by about 4% than protons whereas at Ld = 6 cm, RBE of protons is higher by about 13% than antiprotons. Significance. The study shows that antiproton radiotherapy is advantageous as compared to protons considering enhancements in the absorbed dose and RBE-weighed dose values at the Bragg-peak.

Microdosimetry of an accelerator based thermal neutron field for Boron Neutron Capture Therapy

The MUNES project (MUltidisciplinary NEutron Source) aims at the realization of an intense accelerator-based source of thermal neutrons, suitable for Boron Neutron Capture Therapy (BNCT). This exploits the interaction of 5 MeV protons onto a beryllium target, producing a fast neutron spectrum, which is moderated to the thermal range by a large assembly made of a Polytetrafluoroethylene (PTFE) tank filled with heavy water, surrounded by graphite blocks. The thermal neutron field is extracted through a bismuth beam port. The microdosimetric characterization of this field was performed using a cylindrical avalanche-confinement Tissue Equivalent Proportional Counter (TEPC) equipped with interchangeable cathode walls, positioned in front of the beam port. Measurements were taken both with a boron-doped wall and with an undoped one. The comparison of the two microdosimetric distributions allows to distinguish the relative dose contribution due to alpha particles and lithium ions from the BNC reaction from that of photons and other particles from neutron interactions on the cathode walls. The Relative Biological Effectiveness (RBE) was also calculated from the convolution of the measured spectra with a biological weighting function. This paper describes the experimental microdosimetric approach and the results of measurements with a boron-loaded cathode performed for the first time at an accelerator-based BNCT source.

Theoretical and experimental estimation of the relative optically stimulated luminescence efficiency of an optical-fiber-based BaFBr:Eu detector for swift ions

ABSTRACT The reliability of dose assessment with radiation detectors is an important feature in various fields, such as radiotherapy, radiation protection, and high-energy physics. However, many detectors irradiated by high linear energy transfer (LET) radiations exhibit decreased efficiency called the quenching effect. This quenching effect depends not only on the particle LET but also strongly on the ion species and its microscopic pattern of energy deposition. Recently, a computational method for estimating the relative efficiency of luminescence detectors has been proposed following the analysis of microdosimetric specific energy distributions simulated using the particle and heavy ion transport code system (PHITS). This study applied the model to estimate the relative optically stimulated luminescence (OSL) efficiency of BaFBr:Eu detectors. Additionally, we measured the luminescence intensity of BaFBr:Eu detectors exposed to 4He, 12C, and 20Ne ions to verify the calculated data. The model reproduced the experimental data in the cases of adopting a microdosimetric target diameter of approximately 30–50 nm. The calculated relative efficiency exhibits ion-species dependence in addition to LET. This result shows that the microdosimetric calculation from specific energy is a successful method for accurately understanding the results of OSL measurements with BaFBr:Eu detectors irradiated by various particles.

TISSUE-EQUIVALENCE OF H2 GAS FOR MICRODOSIMETRY IN NEUTRON FIELDS: A GEANT4 MONTE CARLO STUDY.

Hydrogen (H2) as filling gas in Tissue-equivalent proportional counter (TEPC) for measurements of microdosimetric distributions in neutron fields is investigated using the Monte Carlo-based Geant4 toolkit. The neutron fields considered are monoenergetic neutrons (1keV-14MeV) and ISO reference neutron sources 241Am-Be, 241Am-B, 252Cf and 252Cf+D2O. Based on the energy deposited in the gas cavities (tissue-equivalent (TE) propane and H2) of the TEPC, density scaling correction, ${f}_{\rho }$, to be applied on H2 gas to achieve tissue-equivalence is calculated for the above sources at 1μm site size. The calculated value of ${f}_{\rho }$ for the ISO-neutron sources is 0.40, which suggests that energy deposition in the gas cavities is predominantly due to crossers. In the case of monoenergetic neutrons, depending upon the energy, ${f}_{\rho }$ is in the range of 0.11-0.45. The study shows that the TE propane and H2-based microdosimetric distributions are comparable when the density of H2 is scaled appropriately. Mean quality factor $\overline{Q}$ calculated based on microdosimetric distribution increases initially with neutron energy up to 100keV and thereafter decreases with energy. Depending upon the neutron energy, TE propane and H2-based $\overline{Q}$ values are comparable to within 3-15%, and for the ISO sources, the comparison is within 5-8%. For the ISO neutron sources, $\overline{Q}$ values are in the range of ~10-15.

Microdosimetry and Dose-Averaged LET Calculations of Protons in Liquid Water: A Novel Geant4-DNA Application

The spatial distribution of energy deposition events is an essential aspect in the determination of the radiobiological effects of ionizing radiation at the cellular level. Microdosimetry provides a theoretical framework for the description of these events, and has been used in several studies to address problems such as the characterization of Linear Energy Transfer (LET) and Relative Biological Effectiveness (RBE) of ion beams for proton therapy applications. Microdosimetry quantities and their distributions can be obtained by means of Monte Carlo simulations. In this work, we present a track structure Monte Carlo (MC) application, based on Geant4-DNA, for the computation of microdosimetric distributions of protons in liquid water. This application provides two sampling methods uniform and weighted, for the scoring of the quantities of interest in spherical sites, with diameters ranging from 1 to 10 μm. As an element of novelty, the work shows the approach followed to calculate, without resorting to dedicated simulations, the distribution of energy imparted to the site per electronic collision of the proton, which can be used to obtain the macroscopic dose-averaged LET as proposed by Kellerer. Furthermore, in this work the concept of effective mean chord length is proposed to take into account δ-ray influx and escape in the calculation of macroscopic dose-averaged LET for proton track segments and retrieve the agreement predicted by Kellerer’s formula. Finally, the results obtained demonstrate that our MC application is reliable and computational-efficient to perform calculations of microdosimetric distributions and dose-averaged LET of proton track segments in liquid water.

The microdosimetric one-hit detector model for calculating the relative efficiency of the alanine pellet dosimeter in low energy X-ray beams

The alanine pellet dosimeter is a widely used reference dosimeter in both medical and industrial dosimetry across a wide range of beam qualities. A challenge when using alanine in low energy X-ray beams is its strong energy dependence; a significant decline is observed in the alanine response per dose-to-water relative to irradiations in a cobalt-60 reference field. This decrease is caused by the physical difference in alanine to water dose ratios combined with a radiochemical decrease in the intrinsic detector efficiency but is difficult to characterize mainly due to experimental uncertainties.Here we have applied a microdosimetric one-hit detector model to characterize the intrinsic detector efficiency of the alanine pellet dosimeter in low energy X-ray beams. Microdosimetric distributions were estimated from track structure calculations using the Geant4-DNA Monte Carlo software, where literature data was used to determine free model parameters.The model was applied to two sets of X-ray spectra with low (40 kV to 170 kV) and medium (100 kV to 300 kV) tube potential, covering a wide range of beam qualities. A relative detector efficiency of 0.937 was obtained for the low energy set with variations between −1.0% and 1.5%, whereas the efficiency varied between approximately 0.925 and 0.985 for the medium energy set, with a strong correlation to the half-value layer of the beam.It is concluded, that the half-value layer of an X-ray beam is not sufficient characterization to uniquely determine the relative efficiency of an alanine pellet dosimeter. However, the variation in relative efficiency with respect to the half-value layer is small.

Patient-specific microdosimetry: a proof of concept

Microscopic energy deposition distributions from ionizing radiation vary depending on biological target size and are used to predict the biological effects of an irradiation. Ionizing radiation is thought to kill cells or inhibit the cell cycle mainly by damaging DNA in the cell nucleus. The size of cells and nuclei depends on tissue type, cell cycle, and malignancy, all of which vary between patients. The aim of this study was to develop methods to perform patient-specific microdosimetry, that being, determining microdosimetric quantities in volumes that correspond to the sizes of cells and nuclei observed in a patient’s tissue. A histopathological sample extracted from a stage I lung adenocarcinoma patient was analyzed. A pouring simulation was used to generate a three-dimensional tissue model from cell and nucleus size information determined from the histopathological sample. Microdosimetric distributions including and were determined for and in a patient-specific model containing a distribution of cell and nucleus sizes. Fixed radius models and a summation method were compared to the full patient-specific model to evaluate their suitability for fast determination of patient-specific microdosimetric parameters. In the summation method, f(y) from many fixed radii models are summed. Fixed radius models do not provide a close approximation of the full patient-specific model or for the lower energy sources investigated, and The higher energy sources investigated, and are less sensitive to target size variation than and The summation method yields the most accurate approximation of the full model for all radioisotopes investigated. The use of a summation method allows for the computation of patient-specific microdosimetric distributions with the computing power of a personal computer. With appropriate biological inputs the microdosimetric distributions computed using these methods can yield a patient-specific relative biological effectiveness as part of a multiscale treatment planning approach.

Repeatability and Reproducibility of Microdosimetry With a Mini-TEPC

Experimental microdosimetry measures the energy deposited in a microscopic sensitive volume (SV) by single ionizing particles traversing the SV or passing by. The fundamental advantage of experimental microdosimetry over the computational approach is that the first allows to determine distributions of energy deposition when information on the energy and nature of the charged particles at the point of interest is incomplete or fragmentary. This is almost always the case in radiation protection applications, but discrepancies between the modelled and the actual scenarios should be considered also in radiation therapy. Models for physical reality are always imperfect and rely both on basic input data and on assumptions and simplifications that are necessarily implemented. Furthermore, unintended events due to human errors or machine/system failures can be minimized but cannot be completely avoided.Though in proton radiation therapy (PRT) a constant relative biological effectiveness (RBE) of 1.1 is assumed, there is evidence of an increasing RBE towards the end of the proton penetration depth. Treatment Planning Systems (TPS) that take into account a variable linear energy transfer (LET) or RBE are already available and could be implemented in PRT in the near future. However, while the calculated dose distributions produced by the TPS are routinely verified with ionization chambers as part of the quality assurance program of every radiotherapy center, there is no commercial detector currently available to perform routine verification of the radiation quality, calculated by the TPS through LET or RBE distributions. Verification of calculated LET is required to make sure that a complex robustly optimized plan will be delivered as planned. The scientific community is coming to conclusion that a new domain of Quality Assurance additionally to the physical dose verification is required, and microdosimetry can be the right approach to address that. A first important prerequisite is the repeatability and reproducibility of microdosimetric measurements. This work aims at studying experimentally the repeatability and reproducibility of microdosimetric measurements performed with a miniaturized Tissue Equivalent Proportional Counter (mini-TEPC) in a 62 MeV proton beam. Experiments were carried out within 1 year and without propane gas recharging and by different operators. RBE was also calculated by applying the Loncol’s weighting function r(y) to microdosimetric distributions. Demonstration of reproducibility of measured microdosimetric quantities y¯F, y¯D and RBE10 in 62 MeV proton beam makes this TEPC a possible metrological tool for LET verification in proton therapy. Future characterization will be performed in higher energy proton beams.

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.

Microdosimetry-based relative biological effectiveness calculations for radiotherapeutic electron beams: a FLUKA-based study.

Based on FLUKA, the present study is aimed at calculating the microdosimetric distributions of electron beams (6, 12 and 18MeV) for radiotherapy as a function of depth in water at a site-size of 1μm using a tissue-equivalent proportional counter (TEPC). Using the calculated microdosimetric distributions, the depth-specific relative biological effectiveness (RBE) of electron beams used in radiotherapy is calculated based on the theory of dual radiation action (TDRA) and the microdosimetric kinetic model (MKM). The TDRA-based calculation shows the variation of RBE of an electron beamwith the absorbed dose and depth in water. In this study, we compared the RBE values calculated based on the TDRA and MKM. The FLUKA-based microdosimetric distributions in water obtained using the pre-calculated electron fluence spectra resulted in an improvement in the computational efficiency by a factor of 110 when compared with a full simulation. Depending on the beam energy and depth of water, RBETDRA was in the range 0.67-0.78. RBEMKM at 10% survival of HSG tumor cells was 0.84, which was nearly independent of the depth and beam energy.

Microdosimetry in low energy proton beam at therapeutic-equivalent fluence rate with silicon 3D-cylindrical microdetectors

In this work we show the first microdosimetry measurements on a low energy proton beam with therapeutic-equivalent fluence rates by using the second generation of 3D-cylindrical microdetectors. The sensors belong to an improved version of a novel silicon-based 3D-microdetector design with electrodes etched inside silicon, which were manufactured at the National Microelectronics Centre (IMB-CNM, CSIC) in Spain. A new microtechnology has been employed using quasi-toroid electrodes of 25 μm diameter and a depth of 20 μm within the silicon bulk, resulting in a well-defined cylindrical radiation sensitive volume. These detectors were tested at the 18 MeV proton beamline of the cyclotron at the National Accelerator Centre (CNA, Spain). They were assembled into an in-house low-noise readout electronics to assess their performance at a therapeutic-equivalent fluence rate. Microdosimetry spectra of lineal energy were recorded at several proton energies starting from 18 MeV by adding 50 μm thick tungsten foils gradually at the exit-window of the cyclotron external beamline, which corresponds to different depths along the Bragg curve. The experimental values in silicon cover from (5.7 ± 0.9) to (8.5 ± 0.4) keV μm−1 in the entrance to (27.4 ± 2.3) keV μm−1 in the distal edge. Pulse height energy spectra were crosschecked with Monte Carlo simulations and an excellent agreement was obtained. This work demonstrates the capability of the second generation 3D-microdetectors to assess accurate microdosimetric distributions at fluence rates as high as those used in clinical centers in proton therapy.