Frequency-mean Specific Energy Research Articles

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.

Calculation of microdosimetric spectra for protons using Geant4-DNA and a μ-randomness sampling algorithm for the nanometric structures

Purpose Through introducing stochastic quantities that can be connected to the dimensions of the microscopic structures exposed to radiations, microdosimetry is concerned with the substantive specifications of radiation quality that could help gain insight into radiation effects. Utilizing the μ-randomness method and Geant4-DNA code, we calculated microdosimetry quantities for nanometric structures in a spherical body of water irradiated with protons. To gain more insight into the effects of radiation on microscopic structures and validate the code parameters, we made a comparison between our results obtained within Geant4-DNA and results from other simulations. Materials and methods We calculated microdosimetric quantities through irradiating a spherical body of water of 6 μm diameter with 0.5–100 MeV protons. Microdosimetric quantities were derived for cylinders with diameter × height values of 23 × 23, 50 × 100, and 300 × 300 Å × Å, which would resemble the typical sizes of sub-cellular organisms such as the DNA, nucleosome, and chromatin fiber. We exploited the concept of μ-randomness to introduce convex bodies of random positions and directions for calculating microdosimetric quantities. We used the Geant4-DNA Monte Carlo simulation toolkit for transporting protons and secondary particles and calculating the frequency- and dose-mean lineal and specific energies in cylindrical volumes. Specifically, for same-sized cylindrical volumes, microdosimetric parameters obtained by Nikjoo et al. using the KURBUC code were used for evaluation. Results For the energy range investigated, the frequency-mean lineal energy, dose-mean lineal energy, frequency-mean specific energy, and dose-mean specific energy vary within [2.34,47.06] (keV/μm), [10.40,68.55] (keV/μm), [0.04,39.38] × 106 cGy, and [0.16,90.29] × 106 cGy, respectively. Regardless of the proton energy, our specific-energy results showed higher sensitivity to volume change, for smaller cylinder volumes rather than larger ones. Regardless of both proton energy and volume of the cylinder under study, we observed a generally better agreement between our frequency-mean, than dose-mean, specific energy results and the KURBUC results. Conclusion Using Geant4-DNA to account for the stochastic nature of energy depositions due to physical interactions between radiation and matter, we calculated microdosimetry parameters concerning proton irradiation. By employing microdosimetry concepts in conjunction with simulation results of our previous work on radiation effects on the DNA, we pinpointed and quantified correlations between microdosimetry parameters and DNA damage. As such, for a volume with comparable mass and mean chord length to the DNA, we could observe the clear correspondence of the mean lineal and specific energy results with the double-strand-break yields of protons in Gy−1.Gbp−1.

Monte Carlo simulations of ³He ion physical characteristics in a water phantom and evaluation of radiobiological effectiveness.

(3)He ions may hold great potential for clinical therapy because of both their physical and biological properties. In this study, the authors investigated the physical properties, i.e., the depth-dose curves from primary and secondary particles, and the energy distributions of helium ((3)He) ions. A relative biological effectiveness (RBE) model was applied to assess the biological effectiveness on survival of multiple cell lines. In light of the lack of experimental measurements and cross sections, the authors used Monte Carlo methods to study the energy deposition of (3)He ions. The transport of (3)He ions in water was simulated by using three Monte Carlo codes-FLUKA, GEANT4, and MCNPX-for incident beams with Gaussian energy distributions with average energies of 527 and 699 MeV and a full width at half maximum of 3.3 MeV in both cases. The RBE of each was evaluated by using the repair-misrepair-fixation model. In all of the simulations with each of the three Monte Carlo codes, the same geometry and primary beam parameters were used. Energy deposition as a function of depth and energy spectra with high resolution was calculated on the central axis of the beam. Secondary proton dose from the primary (3)He beams was predicted quite differently by the three Monte Carlo systems. The predictions differed by as much as a factor of 2. Microdosimetric parameters such as dose mean lineal energy (y(D)), frequency mean lineal energy (y(F)), and frequency mean specific energy (z(F)) were used to characterize the radiation beam quality at four depths of the Bragg curve. Calculated RBE values were close to 1 at the entrance, reached on average 1.8 and 1.6 for prostate and head and neck cancer cell lines at the Bragg peak for both energies, but showed some variations between the different Monte Carlo codes. Although the Monte Carlo codes provided different results in energy deposition and especially in secondary particle production (most of the differences between the three codes were observed close to the Bragg peak, where the energy spectrum broadens), the results in terms of RBE were generally similar.

Extension of TOPAS for the simulation of proton radiation effects considering molecular and cellular endpoints

The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients.TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring conditions. Expert users may further extend TOPAS scoring capabilities by plugging in their own additional C++ code. This structure was utilized for the implementation of eight biophysical models suited to calculate proton RBE. As far as physics parameters are concerned, four of these models are based on the proton linear energy transfer, while the others are based on DNA double strand break induction and the frequency-mean specific energy, lineal energy, or delta electron generated track structure. The biological input parameters for all models are typically inferred from fits of the models to radiobiological experiments.The model structures have been implemented in a coherent way within the TOPAS architecture. Their performance was validated against measured experimental data on proton RBE in a spread-out Bragg peak using V79 Chinese Hamster cells.This work is an important step in bringing biologically optimized treatment planning for proton therapy closer to the clinical practice as it will allow researchers to refine and compare pre-defined as well as user-defined models.

A Monte Carlo evaluation of carbon and lithium ions dose distributions in water

Purpose: To compare dose distributions on the central- and off-axis for 12C and 7Li ion beams simulated by the codes SHIELD-HIT (Heavy Ion Transport) and FLUKA (FLUKtuierende KAskade), and compare with experimental data for 300 MeV/u 12C and 185 MeV/u 7Li ion beams.Materials and methods: The general purpose Monte Carlo codes, SHIELD-HIT10 and FLUKA 2008.3d.1 were used for the ion dose distribution calculations. SHIELD-HIT transports hadrons and atomic nuclei of arbitrary charge and mass number in an energy range from 1 keV/u up to 1 GeV/u. Similarly, FLUKA transports charged hadrons in an energy range from 100 keV up to 20 TeV. Neutrons are transported down to thermal energies in both codes. Inelastic nuclear interactions are modelled in SHIELD-HIT by the Many Stage Dynamical Model (MSDM), whereas in FLUKA the Pre-Equilibrium Approach to Nuclear Thermalisation (PEANUT) package which includes a Generalized Intra-Nuclear Cascade model was used.Results: The dose distributions in water irradiated with 300 MeV/u 12C and 185 MeV/u 7Li ion beams were simulated with the two codes. Studies were performed of the energy deposition both on the central axis and at lateral distances up to 10 cm off-axis. The dose distributions calculated by SHIELD-HIT and FLUKA were compared with published experimental data. The dose mean lineal energy , frequency mean lineal energy , dose mean specific energy , and frequency mean specific energy were calculated with the ion track-structure code PITS99 (Positive Ion Track Structure 99), coupled with the electron code KURBUC for the primary and secondary ions average energies at 1 mm before the Bragg peak.Conclusion: The Monte Carlo codes show good agreement with experimental results for off-axis dose distributions. The disagreements in the Bragg peak region for the central-axis dose distributions imply that further improvements especially in the nuclear interaction models are required to increase the accuracy of the codes.

Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency–mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

A database of frequency distributions of energy depositions in small-size targets by electrons and ions

Linear energy transfer (LET) is an average quantity, which cannot display the stochastics of the interactions of radiation tracks in the target volume. For this reason, microdosimetry distributions have been defined to overcome the LET shortcomings. In this paper, model calculations of frequency distributions for energy depositions in nanometre size targets, diameters 1-100 nm, and for a 1 μm diameter wall-less TEPC, for electrons, protons, alpha particles and carbon ions are reported. Frequency distributions for energy depositions in small-size targets with dimensions similar to those of biological molecules are useful for modelling and calculations of DNA damage. Monte Carlo track structure codes KURBUC and PITS99 were used to generate tracks of primary electrons 10 eV to 1 MeV, and ions 1 keV µm(-1) to 300 MeV µm(-1) energies. Distribution of absolute frequencies of energy depositions in volumes with diameters of 1-100 nm randomly positioned in unit density water irradiated with 1 Gy of the given radiation was obtained. Data are presented for frequency of energy depositions and microdosimetry quantities including mean lineal energy, dose mean lineal energy, frequency mean specific energy and dose mean specific energy. The modelling and calculations presented in this work are useful for characterisation of the quality of radiation beam in biophysical studies and in radiation therapy.

Understanding of the Microdosimetric Quantities Obtained by a TEPC

A lineal energy, y and a specific energy, z are fundamental microdosimetric quantities for describing a radiation energy deposition event in a microscopic volume simulating a human tissue cell. They can be measured by using a low pressure Tissue Equivalent Proportional Counter (TEPC) with a so-called Bragg-Gray cavity principle. One of the advantages of using a TEPC is that it can directly evaluate a mean quality factor of the neutron in a mixed radiation field from the measured dose-mean lineal energy by applying a quality factor and LET relationship. From this mean quality factor and the absorbed dose estimated in terms of the frequency-mean specific energy, we can further evaluate a neutron dose equivalent for a radiation protection purpose. In this paper were described the results of the lineal and specific energy measurement in the KAERI 252Cf neutron calibration field by a low pressure TEPC system designed and manufactured by the Health Physics Department at KAERI. Mean quality factors and dose equivalents of 252Cf neutron were then evaluated from the measurement results of the lineal and specific energy values

Monte Carlo microdosimetry of 188Re- and 131I-labelled anti-CD20

The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f1(z) in the cell nucleus using the beta spectra of the 188Re and 131I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either 188Re or 131I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9–12%. In general, the antibody radiolabelled with 131I produces single-event distribution functions that yield higher frequency-mean specific energies.

Microdosimetric Model for the Induction of Cell Killing through Medium‐Borne Signals

Microbeam, medium-transfer and low-dose experiments have demonstrated that intercellular signals can initiate many of the same biological events and processes as direct exposure to ionizing radiation. These phenomena cast doubt on cell-autonomous modes of action and the linear, no-threshold carcinogenesis paradigm. To account for the effects of intercellular signals, new approaches are needed to relate dosimetric quantities to the emission and processing of signals by irradiated and unirradiated cells. In this paper, microdosimetric principles are used to develop a stochastic model to relate absorbed dose to the emission and processing of cell death signals by unirradiated cells. Our analyses of published results of medium transfer experiments performed using HPV-G human keratinocytes suggest that the emission of death signals is a bi-exponential function of dose with a distinct plateau in the 5- to 100-mGy range. However, the emission of death signals by HPV-G cells may not become fully saturated until the absorbed dose becomes larger than 0.6 Gy. Similar saturation effects have been observed in microbeam and medium-transfer experiments with other mammalian cell lines. The model predicts that the cell-killing effect of medium-borne death signals decreases exponentially as the absorbed dose becomes small compared to the frequency-mean specific energy per radiation event.

Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy

Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy.

Microdosimetry of astatine-211 single-cell irradiation: Role of daughter polonium-211 diffusion

A microdosimetric analysis of previously published data on 211At-albumin, free 211At, and 211At-C215 irradiation of Colo-205 cells in a slowly rotating single-cell suspension is presented. A custom-built computer program based on the Monte Carlo method was used to simulate the irradiation and the energy deposition in individual cell nuclei. Separate simulations were made for the assumption that the 211Po atom stays in the position where it is created, and that it diffuses away. The mean event number at which 37% of all cells survived, n37, and the frequency mean specific energy per event, zF, were estimated. The Poisson distribution of events and simulated single and multievent distributions of specific energy were used to find the single-cell specific energy at which the probability of survival is reduced to 37%, z37. The calculated single-cell radiosensitivity values show that 211Po atoms, created on a cell surface by the decay of 211At atoms, will diffuse from the cell during its life-span. The increasing distance to the cell nucleus will drastically decrease the probability of the emitted alpha particle to hit the nucleus. This will result in fewer alpha-particle events in the cell nucleus. For dispersed cells, the diffusion of 211Po atoms will reduce the total dose from cell-bound 211At by a factor of 2.

Microdosimetric properties of ionizing electrons in water: a test of the PENELOPE code system

The ability to simulate the tortuous path of very low-energy electrons in condensed matter is important for a variety of applications in radiobiology. Event-by-event Monte Carlo codes such as OREC, MOCA and PITS represent the preferred method of computing distributions of microdosimetric quantities. However, event-by-event Monte Carlo is computationally expensive, and the cross sections needed to transport simulations to this level of detail are usually only available for water. In the recently developed PENELOPE code system, ‘hard’ electron and positron interactions are simulated in a detailed way while ‘soft’ interactions are treated using multiple scattering theory. Using this mixed simulation algorithm, electrons and positrons can be transported down to energies as low as 100 eV. To our knowledge, PENELOPE is the first widely available, general purpose Monte Carlo code system capable of transporting electrons and positrons in arbitrary media down to such low energies. The ability to transport electrons and positrons to such low energies opens up the possibility of using a general purpose Monte Carlo code system for microdosimetry.This paper presents the results of a code intercomparison study designed to test the applicability of the PENELOPE code system for microdosimetry applications. For sites comparable in size to a mammalian cell or cell nucleus, single-event distributions, site-hit probabilities and the frequency-mean specific energy per event are in reasonable agreement with those predicted using event-by-event Monte Carlo. Site-hit probabilities and the mean specific energy per event can be estimated to within about 1–10% of those predicted using event-by-event Monte Carlo. However, for some combinations of site size and source-target geometry, site-hit probabilities and the mean specific energy per event may only agree to within 25–60%. The most problematic source-target geometry is one in which the emitted electrons are very close to the tally site (e.g., a point source on the surface of a cell). Although event-by-event Monte Carlo will continue to be the method of choice for microdosimetry, PENELOPE is a useful, computationally efficient tool for some classes of microdosimetry problem. PENELOPE may prove particularly useful for applications that involve radiation transport through materials other than water or for applications that are too computationally intensive for event-by-event Monte Carlo, such as in vivo microdosimetry of spatially complex distributions of radioisotopes inside the human body.

A theoretical model for event statistics in microdosimetry. I: Uniform distribution of heavy ion tracks.

In this work we describe a novel approach to solving microdosimetry problems using conditional probabilities and geometric concepts. The intersection of a convex site with a field of randomly oriented straight track segments is formulated in terms of the relative overlap between the chord associated with the action line of the track and the track itself. This results in a general formulation that predicts the contribution of crossers, stoppers, starters, and insiders in terms of two separate functions: the chord length distribution (characteristic of the site geometry and the type of randomness) and an independent set of conditional probabilities. A Monte Carlo code was written in order to validate the proposed approach. The code can represent the intersection between an isotropic field of charged particle tracks and a general ellipsoid of unrestricted geometry. This code was used to calculate the event distribution for a sphere as well as the expected mean value and variance of the track length distribution and to compare these against the deterministic calculations. The observed agreement was shown to be very good, within the precision of the Monte Carlo approach. The formulation is used to calculate the event frequency, lineal energy, and frequency mean specific energy for several monoenergetic and isotropic proton fields in a spherical site, as a function of the site diameter, proton energy, and the event type.

Microdosimetry near the Trajectory of High-Energy Heavy Ions

Single-event energy distributions were measured in a 1.3-micron-diameter site as a function of radial distance from the trajectory of high-energy iron ions having an energy of about 600 MeV/amu. It was found that beyond distances of a few micrometers the average lineal energy of the (mostly single) secondary electrons (delta rays) is of the order of 3 keV/micron. This is similar to the value found in a medium irradiated by 170-keV photons. The frequency-mean specific energy for delta rays occurring at large distances from the path of the primary ion exceeds the calculated (radial) absorbed dose by two orders of magnitude.