keV Μm Research Articles

Adaptation of stochastic microdosimetric kinetic model to hypoxia for hypo-fractionated multi-ion therapy treatment planning

For hypo-fractionated multi-ion therapy (HFMIT), the stochastic microdosimetric kinetic (SMK) model had been developed to estimate the biological effectiveness of radiation beams with wide linear energy transfer (LET) and dose ranges. The HFMIT will be applied to radioresistant tumors with oxygen-deficient regions. The response of cells to radiation is strongly dependent on the oxygen condition in addition to radiation type, LET and absorbed dose. This study presents an adaptation of the SMK model to account for oxygen-pressure dependent cell responses, and develops the oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model. In the model, following assumptions were made: the numbers of radiation-induced sublethal lesions (double-strand breaks) are reduced due to lack of oxygen, and the numbers of oxygen-mediated lesions are reduced for radiation with high LET. The model parameters were determined by fitting survival data under aerobic and anoxic conditions for human salivary gland tumor cells and V79 cells exposed to helium-, carbon-, and neon-ion beams over the LET range of 18.5–654.0 keV μm−1. The OSMK model provided good agreement with the experimental survival data of the cells with determination coefficients >0.9. In terms of oxygen enhancement ratio, the OSMK model reproduced the experimental data behavior, including slight dependence on particle type at the same LET. The OSMK model was then implemented into the in-house treatment planning software for the HFMIT to validate its applicability in clinical practice. A treatment plan with helium- and neon-ion beams was made for a pancreatic cancer case assuming an oxygen-deficient region within the tumor. The biological optimization based on the OSMK model preferentially placed the neon-ion beam to the hypoxic region, while it placed both helium- and neon-ion beams to the surrounding normoxic region. The OSMK model offered the accuracy and usability required for hypoxia-based biological optimization in HFMIT treatment planning.

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.

Radiochromic film dosimetry for protons up to 10 MeV with EBT2, EBT3 and unlaminated EBT3 films

Passive dosimetry with radiochromic films is widely used in proton radiotherapy, both in clinical and scientific environments, thanks to its simplicity, high spatial resolution and dose-rate independence. However, film under-response for low-energy protons, the so-called linear-energy transfer (LET) quenching, must be accounted and corrected for. We perform a meta-analysis on existing film under-response data with EBT, EBT2 and EBT3 GAFchromic™ films and provide a common framework to integrate it, based on the calculation of dose-averaged LET in the active layer of the films. We also report on direct measurements with the 10 MeV proton beam at the Center for Microanalysis of Materials (CMAM) for EBT2, EBT3 and unlaminated EBT3 films, focusing on the 20–80 keV μm−1 LET range, where previous data was scarce. Measured film relative efficiency (RE) values are in agreement with previously reported data from the literature. A model on film RE constructed with combined literature and own experimental values in the 5–80 keV μm−1 LET range is presented, supporting the hypothesis of a linear decrease of RE with LET, with no remarkable differences between the three types of films analyzed.

Exploratory Investigation of Dose-Linear Energy Transfer (LET) Volume Histogram (DLVH) for Adverse Events Study in Intensity Modulated Proton Therapy (IMPT).

We proposed a novel tool-a dose linear energy transfer (LET)-volume histogram (DLVH)-and performed an exploratory study to investigate rectal bleeding in prostate cancer treated with intensity modulated proton therapy. The DLVH was constructed with dose and LET as 2 axes, and the normalized volume of the structure was contoured in the dose-LET plane as isovolume lines. We defined the DLVH index, DLv%(d,l) (ie, v% of the structure) to have a dose of ≥d Gy and an LET of ≥l keV/μm, similar to the dose-volume histogram index Dv%. Nine patients with prostate cancer with rectal bleeding (Common Terminology Criteria for Adverse Events grade ≥2) were included as the adverse event group, and 48 patients with no complications were considered the control group. A P value map was constructed by comparison of the DLVH indices of all patients between the 2 groups using the Mann-Whitney U test. Dose-LET volume constraints (DLVCs) were derived based on the P value map with a manual selection procedure facilitated by Spearman's correlation tests. The obtained DLVCs were further cross-validated using a multivariate support vector machine (SVM)-based normal tissue complication probability (NTCP) model with an independent testing data set composed of 8 adverse event and 13 control patients. We extracted 2 DLVC constraints. One DLVC was obtained, Vdose/LETboundary:2.5keVμmat 75 Gy to 3.2keVμmat8.65Gy <1.27% (DLVC1), revealing a high LET volume effect. The second DLVC, V(72.2Gy,0keVμm) < 2.23% (DVLC2), revealed a high dose volume effect. The SVM-based NTCP model with 2 DLVCs provided slightly superior performance than using dose only, with an area under the curve of 0.798 versus 0.779 for the testing data set. Our results demonstrated the importance of rectal "hot spots" in both high LET (DLVC1) and high dose (DLVC2) in inducing rectal bleeding. The SVM-based NTCP model confirmed the derived DLVCs as good predictors for rectal bleeding when intensity modulated proton therapy is used to treat prostate cancer.

Fast neutron energy based modelling of biological effectiveness with implications for proton and ion beams

A practical neutron energy dependent RBE model has been developed, based on the relationship between a mono-energetic neutron energy and its likely recoil proton energy. Essentially, the linear energy transfer (LET) values of the most appropriate recoil proton energies are then used to modify the linear quadratic model radiosensitivities (α and β) from their reference LET radiation values to provide the RBE estimates. Experimental neutron studies published by Hall (including some mono-energetic beams ranging from 0.2 to 15 MeV), Broerse, Berry, and data from the Clatterbridge and Detroit clinical neutron beams, which all contain some data from a spectrum of neutron energies, are used to derive single effective neutron energies (NEeff) for each spectral beam. These energies yield a recoil proton spectrum, but with an effective mean proton energy (being around 50% of NEeff). The fractional increase in LET is given by the recoil proton LET divided by the proton (LETU) value which provides the highest RBE. This ratio is then used to determine the change in the linear-quadratic model α and β parameters, from those of the reference radiation, to estimate the RBE. The predicted proton recoil RBE is then reasonably close to the experimental neutron RBE values found when taking into account the variation inherent in biological experiments. The work has some important consequences. The data of Hall et al (1975 Radiat. Res. 64 245–55) shows that the highest RBE values are found with neutron energies around 0.3–0.4 MeV, but this energy cannot possibly generate recoil proton energies which are higher, as necessary for a 0.68 MeV proton with a 30.5 keV μm−1 LETU (the LET value which provides the maximum obtainable RBE for a specified ion). For 0.4 MeV neutrons with proton recoil energies of around 0.2 MeV, the latter have a LET of around 62.88 keV μm−1. This could have an impact on proton beam RBE modelling. However, this is compensated by finding that the maximum radiosensitivity for mono-energetic neutrons was around 1.7 times larger than previously suggested from experimental ion beam studies, probably due to the necessary spreading out of Bragg peaks for ion beam experimental purposes, sampling errors and particle range considerations. This semi-empirical model can be used with minimal computer support and could have applications in ionic beams and in radioprotection.

The study of radium and polonium sorption by a thin-layer MnO2-CTA sorbent

The work focuses on sorption of radium-223 and polonium-210 by a thin-layer MnO2-CTA sorbent. The maximal sorption of Ra (≈ 80%) and Po (≈ 12%) was achieved after 1 day of sorption. For Ra, decrease of quality of alpha spectrum was observed during sorption that can be explained by its diffusion into MnO2 and support layers. The average thickness of the sorption layer was determined to be 456 nm, whereas the energy loss of 5 MeV α-particles in MnO2 is approximately 270 keV μm−1. Scanning electronic microscopy and optical microphotographs confirmed flat morphology of the sorbent’s surface and no morphology changes as a result of sorption. In contrast to radium, the values of full width at half maximum (FWHM) of the 210Po alpha peak just slightly increased from ≈ 40 to ≈ 80 keV after 2 weeks of sorption that can be explained by larger ionic radius of polonium and another sorption mechanism, which is probably a partial replacement of manganese by polonium in the manganese dioxide crystal lattice. The observed phenomenon of increasing FWHM of alpha peaks from flat sorbents was suggested as an instrument for study the diffusion of alpha emitters in flat sorption-active layers.

Infrared analysis of Glycine dissociation by MeV ions and keV electrons

ABSTRACT Knowledge on amino acid’s dissociation rates by solar wind is relevant for the study of biomaterial resistance in space. The radiolysis and sputtering of glycine by 1 keV electron beam and by 1.8 MeV H+, 1.5 MeV He+, and 1.5 MeV N+ ion beams are studied in laboratory at room temperature. Infrared spectroscopy is used to determine column density decrease rates and destruction cross-sections. Present results stand in good agreement with those found in the literature and show that over five orders of magnitude, apparent destruction cross-sections (which includes sputtering), σdap, are approximately proportional to the electronic stopping power, Se, that is σdap ≈ aSe, where 1/a ≈ 120 eV nm−3. This value corresponds to the mean absorbed energy density necessary to dissociate (and/or eject) glycine; if it is taken as the minimum energy for molecular destruction, than the stopping power threshold is 23 keV μm−1. Assuming σdap = aSe for electron and ion projectiles, the half-life of pure α-glycine is estimated for the solar wind processing at 1 au: about 10 D for protons or electrons and 40 D for He ions.

Development of a new microdosimetric biological weighting function for the RBE10 assessment in case of the V79 cell line exposed to ions from 1H to 238U

An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in case of exposure to various types of ions from 1H to 238U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer range of almost five orders of magnitude (0.2 keV µm−1 to 15 000 keV µm−1 in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ∼14%. The IBWF results were also compared with corresponding calculations (in vitro RBE10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE10 for the V79 cell line in case of ions heavier than 20Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with eight different microdosimeters in 19 1H and 12C beams at ten different facilities (eight clinical and two research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low-density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in case of computer-simulated microdosimetric spectra (average relative deviation equal to 0.8% and 5.7% for 1H and 12C ions respectively).

Proton monoenergetic arc therapy (PMAT) to enhance LETd within the target

We show the performance and feasibility of a proton arc technique so-called proton monoenergetic arc therapy (PMAT). Monoenergetic partial arcs are selected to place spots at the middle of a target and its potential to enhance the dose-averaged linear energy transfer (LETd) distribution within the target. Single-energy partial arcs in a single 360 degree gantry rotation are selected to deposit Bragg’s peaks at the central part of the target to increase LETd values. An in-house inverse planning optimizer seeks for homogeneous doses at the target while keeping the dose to organs at risk (OARs) within constraints. The optimization consists of balancing the weights of spots coming out of selected partial arcs. A simple case of a cylindrical target in a phantom is shown to illustrate the method. Three different brain cancer cases are then considered to produce actual clinical plans, compared to those clinically used with pencil beam scanning (PBS). The relative biological effectiveness (RBE) is calculated according to the microdosimetric kinetic model (MKM). For the ideal case of a cylindrical target placed in a cylindrical phantom, the mean LETd in the target increases from 2.8 keV μm−1 to 4.0 keV μm−1 when comparing a three-field PBS plan with PMAT. This is replicated for clinical plans, increasing the mean RBE-weighted doses to the CTV by 3.1%, 1.7% and 2.5%, respectively, assuming an ratio equal to 10 Gy in the CTV. In parallel, LETd to OARs near the distal edge of the tumor decrease for all cases and metrics (mean LETd, LD,2% and LD,98%). The PMAT technique increases the LETd within the target, being feasible for the production of clinical plans meeting physical dosimetric requirements for both target and OARs. Thus, PMAT increases the RBE within the target, which may lead to a widening of the therapeutic index in proton radiotherapy that would be highlighted for low ratios and hyperfractionated schedules.

Simultaneous determination of the dose and linear energy transfer (LET) of carbon-ion beams using radiochromic films

Radiochromic films are useful as dosimeters in high-precision radiotherapy owing to their high spatial resolution. However, when a particle beam is measured using a radiochromic film, the dose cannot be estimated accurately because the film darkness varies with variations in linear energy transfer (LET). This paper proposes a novel method for estimating the LET and the dose based on the film darkness. In this method, after a high-LET particle beam, such as a carbon-ion beam, was incident on the film, the film was digitized and its net optical density was determined. Further, the non-linearity of the film response curve between the dose and the darkness, depending on LET, was used. Then, calibration curves were created using 290 MeV u−1 mono energetic carbon-ion beams. We used LETs of 20, 50, 100, and 150 keV µm−1 and a physical dose of 2–14 Gy. The calibration curves were approximated for each LET using a quadratic function. The correlations between the coefficients of the quadratic function and the LET were also obtained. To verify the proposed method, the films were irradiated under 12 different conditions corresponding to various depths and doses. Four depths of −2, −5, −10, and −20 mm with respect to the Bragg peak, and three different preset values were used for the film measurements. The films were analyzed in four groups, where each group comprised films irradiated at the same depth. The LETs obtained from the film analysis, ordered from the upstream of the beam, were 20, 41, 56, and 97 keV µm−1, and the doses for the lowest preset value were 3.95, 4.07, 4.03, and 3.99 Gy for the four groups. The LETs obtained from the film analysis increased toward the Bragg peak, and the doses measured in the ionization chamber were almost equal to 4 Gy.

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

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

Nuclear track detector response to energetic heavy ions: study case

Nuclear track methodology (NTM), is employed to analyze PADC detectors response to different energetic ion beams. Due to the passive device linearity response to heavy ions with LET-value > 30 keV μm−1, they are employed in several fields e.g. nuclear industry, medical, environmental radiation and aircraft dosimetry. To further improve application, PADC-detectors were irradiated by beams of 4He (150 MeV nucleon−1), 12C (390 MeV nucleon−1) and 56Fe (465 MeV nucleon−1), in relatively low-dose range ≤ 1 mGy. Results provided, through etched track analysis, valuable information of interest for NTM when high LET ionizing radiation is involved.

Comparison of optical absorption and thermoluminescence in LiF:Mg, TI (TLD-100) following irradiation by high energy protons and 90Sr/90Y beta rays

The optical absorption (OA) energy spectrum and thermoluminescence (TL) glow curve characteristics of LiF:Mg, Ti (TLD-100) samples following 90Sr/90Y beta ray irradiation and high energy proton irradiation are compared for the first time. The beta ray irradiations were carried at room temperature at a dose rate in LiF of approximately 0.13 Gy min−1. Proton irradiations were carried out at energies of 20 MeV, 40 MeV and 58 MeV with initial stopping powers of 5.5, 3.2 and 2.3 keV μm−1 respectively. Proton escaping the TL detectors had average energies 55.9, 37.1, 14.4 MeV and the corresponding stopping power in LiF 2.43, 3.36, 7.19 keV μm−1 respectively. All proton irradiations were carried out at a dose of 1124 Gy in LiF and the beta irradiations at a dose of 970 Gy in LIF. The OA spectra were deconvoluted with Gaussian Peak Shapes using a commercial “Peak-Fit” non-linear curve fitting program from Jandel Scientific. The Gaussian bands are characterized by the two parameters of band energy and width. The glow curves were deconvoluted using the Ben Gurion University mixed-order kinetics program. In the analysis first-order kinetics glow peak shapes were employed. The major difference between the two spectra is in the optical density of the F band at 5.08 eV; 0.17 compared to an average value of 0.33 following beta and proton irradiation respectively. The relative intensity, protons to betas, of the other OA bands are remarkably similar within the experimental errors and indicate that the traps associated with these OA bands are not created by the irradiation. It is demonstrated that proton irradiation of LiF:Mg, Ti (TLD-100) creates F centers with 75% greater efficiency than 90Sr/90Y beta particles. This finding lends further support to the conclusion that track structure theory is unable to accurately predict proton relative efficiencies in LiF:Mg, Ti The results are also interpreted in the framework the spatially correlated trapping center/luminescent center model for composite peak 5 in LiF:Mg,Ti.

Validation of linear energy transfer computed in a Monte Carlo dose engine of a commercial treatment planning system

The relative biological effectiveness (RBE) of protons is highly variable and difficult to quantify. However, RBE is related to the local ionization density, which can be related to the physical measurable dose weighted linear energy transfer (LETD). The aim of this study was to validate the LETD calculations for proton therapy beams implemented in a commercially available treatment planning system (TPS) using microdosimetry measurements and independent LETD calculations (Open-MCsquare (MCS)).The TPS (RayStation v6R) was used to generate treatment plans on the CIRS-731-HN anthropomorphic phantom for three anatomical sites (brain, nasopharynx, neck) for a spherical target (Ø = 5 cm) with uniform target dose to calculate the LETD distribution. Measurements were performed at the University Medical Center Groningen proton therapy center (Proteus Plus, IBA) using a µ+-probe utilizing silicon on insulator microdosimeters capable of detecting lineal energies as low as 0.15 keV µm−1 in tissue. Dose averaged mean lineal energy depth-profiles were measured for 70 and 130 MeV spots in water and for the three treatment plans in water and an anthropomorphic phantom. The measurements were compared to the LETD calculated in the TPS and MCS independent dose calculation engine. D · was compared to D · LETD in terms of a gamma-index with a distance-to-agreement criteria of 2 mm and increasing dose difference criteria to determine the criteria for which a 90% pass rate was accomplished.Measurements of D · were in good agreement with the D · LETD calculated in the TPS and MCS. The 90% passing rate threshold was reached at different D · LETD difference criteria for single spots (TPS: 1% MCS: 1%), treatment plans in water (TPS: 3% MCS: 6%) and treatment plans in an anthropomorphic phantom (TPS: 6% MCS: 1%).We conclude that D · LETD calculations accuracy in the RayStation TPS and open MCSquare are within 6%, and sufficient for clinical D · LETD evaluation and optimization. These findings remove an important obstacle in the road towards clinical implementation of D · LETD evaluation and optimization of proton therapy treatment plans.Novelty and significanceThe dose weighed linear energy transfer (LETD) distribution can be calculated for proton therapy treatment plans by Monte Carlo dose engines. The relative biological effectiveness (RBE) of protons is known to vary with the LETD distribution. Therefore, there exists a need for accurate calculation of clinical LETD distributions. Previous LETD validations have focused on general purpose Monte Carlo dose engines which are typically not used clinically. We present the first validation of mean lineal energy measurements of the LETD against calculations by the Monte Carlo dose engines of the Raystation treatment planning system and open MCSquare.

Microdosimetric characterization of clinical carbon-ion beams using synthetic diamond detectors and spectral conversion methods.

To investigate for the first time the potentialities of obtaining microdosimetric measurements in scanned clinical carbon-ion beams using synthetic single crystal diamond detector and to verify the spectral conversion methods. Microdosimetric measurements were performed at different depths in a water phantom at the therapeutic scanned carbon-ion beam of the National Center of Oncological Hadrontherapy (CNAO) in Pavia, using waterproof encapsulated diamond microdosimeter developed at "Tor Vergata" University. A monoenergetic carbon-ion beam of 195MeV/μ scanned over a square field of 2×2cm2 was used. Experimental microdosimetric spectra were compared with those obtained with a propane-filled Tissue Equivalent Proportional Counters (TEPCs) microdosimeter in the same facility at the same conditions. To this purpose, the spectra in diamond were converted to the spectra that would have been collected with a propane-filled cylindrical sensitive volume by means of a novel analytic methodology, recently developed at MedAustron. The microdosimetric spectra acquired by the diamond microdosimeter show different shapes in the 10keVµm-1 ÷103 keVµm-1 lineal-energy range at different water depths. In spite of the high counting rate, no spectral distortion, due to pile-up events and polarization effects, were observed. The experimental spectra have a low detection threshold of about 6keVµm-1 due to the electronic noise in the irradiation room. The comparison between the spectra converted to propane from diamond detector and the spectra collected directly with propane-filled TEPC shows a good agreement in the whole lineal-energy range. Furthermore this comparison confirms that diamond detector response is LET independent. The frequency- and dose-mean lineal energy values were also assessed for all spectra. The frequency-mean values obtained with diamond microdosimeter at different depths scales rather well with the absorbed dose values. Microdosimetric characterization of a synthetic single crystal diamond detector in high-energy scanned carbon-ion beams was performed. The results of the present study showed that this detector is suitable for microdosimetry of clinical carbon ion beams. In addition, the good agreement between the converted diamond spectra and those obtained with TEPC provides the first experimental validation of the spectra conversion methodologies as valuable tools for the comparison of spectra collected with different detectors.

The experimental dose ranges influence the LETd dependency of the proton minimum RBE (RBEmin)

Cell experiments have shown the proton relative biological effectiveness (RBE) to vary with dose and linear energy transfer (LET), which has led to development of variable RBE models. The RBE is normally estimated from two independent functions, the RBEmax and RBEmin, describing the extreme RBE at low and high doses. While there is consensus that RBEmax increases with increasing LET, the RBEmin is not uniformly defined and its dependency on LET is deviating. In this work, we analysed this dependency and its sensitivity to variations of the experimental dose range.We performed a literature search to find data from existing monoenergetic proton cell survival experiments with (α/β)x values below 5 Gy and dose averaged LET (LETd) values below 20 keV µm−1. From the experiments the doses and their corresponding survival data were extracted. Based on these data, multiple restricted databases were generated by sequential exclusion of low dose data in the experiments followed by a linear-quadratic (LQ) fit. The quadratic component from the LQ-fit was used to estimate RBEmin. The LETd dependency of RBEmin was determined by fitting a linear function to the RBEmin values estimated from the restricted databases.Our analysis showed the LETd dependency of RBEmin to be significantly influenced by the experimental dose range. By including experiments with doses below 1 Gy in the database, we found that RBEmin increased with increasing LETd. By excluding the low dose experiments in our database, the RBEmin became constant for all LETd values. For an LETd value of 5 keV µm−1, a restricted database including the data with the lowest doses gave an RBEmin of 1.4 ± 0.1, while databases with only high dose data (>2 Gy) gave an RBEmin of 1.0 ± 0.1. None of our restricted databases gave a decreasing RBEmin with increasing LETd.Our study showed that RBEmin has a small yet significant dependency on LETd for tissues with low (α/β)x ratio. The LETd dependency of RBEmin varied substantially with the experimental dose range. Including experiments with high minimum dose in RBE models may lead to underestimation of the RBE.

Characterization of a new tissue equivalent proportional counter for dosimetry of neutron and photon fields: comparison of measurements and Monte Carlo simulations

The tissue equivalent proportional counter (TEPC) is widely recognized as an important dosimetric technique particularly for complex radiation fields. The Korea Astronomy and Space Science Institute (KASI) has recently developed a new spherical TEPC to monitor the space radiation environment in the low earth orbit. The purpose of this study is to examine the performance of the TEPC against standard photon (137Cs) and neutron (252Cf) sources through ground-based measurements and Monte Carlo simulations prior to its actual implementation. Lineal energy distributions, microdosimetric spectra and dosimetric quantities for a 2 µm simulated site in pure propane gas were determined for both sources. Both the measured and calculated 137Cs spectra were shown to occur below 11 keV µm−1 that is the typical range covered by photon sources. Complete coincidence of their electron edge regions was also observed. Meanwhile, the proton edge from the measured 252Cf spectra was found to be in good agreement with those from the simulated ones and the literature. The gamma, recoil proton and heavy ions peaks expected for neutron sources were well defined, albeit deviations in the gamma region. The absorbed dose and dose equivalent for both irradiation conditions were also successfully obtained. The dose equivalent for 252Cf was found to be ten times the absorbed dose whereas it remained the same for 137Cs. The discrepancies observed in the low lineal energy region for both irradiation conditions were caused by intrinsic limitations on the experimental set-up and simulation configurations. This mainly contributed to a difference in the measured and calculated dose mean lineal energies of about 4.1% and 8.7% for the photon and neutron cases, respectively. Nevertheless, fair consistency with published data suggested that our TEPC could adequately reproduce the expected microdosimetric distributions for complex radiation fields.

Charged particle radiobiology beamline using tandem accelerator-based MeV protons and carbon ions: a pilot study on the track-end radiation quality, variable biological effectiveness and Bayesian beam dosimetry

For in vitro cell irradiation using tandem accelerator-based MeV protons and carbon ions, by TOPAS simulation, a pilot study of performance evaluation is presented on a collimation beamline for 3 MeV protons and 10 MeV carbon ions from a 2 × 3 MV tandem accelerator. Based on the elements and source parameters, a collimated beam of 2.8 MeV protons or 2.5 MeV carbon ions, with 5.175 mm or 5.166 mm full width tenth maximum (FWTM), respectively, can be delivered to the target cell dish. TOPAS simulations and/or deterministic algorithms present a Bragg curve of linear energy transfer (LET) (10–70 keV μm−1) along a 138 μm range of the proton beam, and a declining LET of the carbon beam (900–100 keV μm−1) within 4 μm range. Based on the biophysical models for relative biological effectiveness (RBE) of protons, TOPAS RBE scorers presents a set of depth-variation curves of the proton RBE (for V79 and DU145 cells), linearly related to the Bragg curve of the proton LET. Based on the microdosimetric-kinetic (MK) theory, in the 4 μm range for a monolayer cell thickness, the mean RBEα (V79 cells) of the carbon ion beam is estimated as 3.612 (late S phase) and 1.737 (G1/S phase) for the mean LET of 492 keV μm−1. For practical irradiations, a tunable proton RBE can be acquired by changing the thickness of the cell dish. For the low-energy high-fluence (rate) beams, indirect beam measurements are proposed to detect the proton-beam induced scattering/recoil protons from a beam-intercepting Mylar film, and the carbon-beam induced backscattered electrons from a gold-deposited Havar-foil beam window. Statistical dosimetry for the indirect measurement is established, using a Bayesian model based on the preset number of detection counts, by which the mean value of the whole-dish dose can be prescribed and the uncertainty introduced in the survival data can be corrected.

On the spectral characterization of radiochromic films irradiated with clinical proton beams

Radiochromic films have been widely studied for clinical dosimetry in conventional external beam radiation therapy. With an increase in practice of proton therapy, such films are being conveniently used; however, their spectroscopic characterization for this modality is lacking. This work investigated the response of the EBT3 radiochromic films irradiated in a Mevion S250™ clinical proton beam. Dose, dose rate, inter-batch, sensitivity, and linear energy transfer (LET) dependencies of the films were studied. Pieces of the radiochromic films from different batches were irradiated using a spread-out Bragg peak (SOBP) proton beam at dose levels between 0.1–15 Gy. Absorption spectra were measured in the wavelength range of 400–800 nm with 2.5 nm resolution. For comparison, the optical density of the films was measured using a flatbed scanner.The net absorbance spectra showed two characteristic absorption bands centered at 636 nm and 585 nm. However, a saturation effect, manifested as broadening/splitting appearance, was observed in the 636 nm band for doses beyond a certain batch-dependent level ~4–10 Gy, in the three different film batches studied. The differences in the spectral shape led to dose-response curves with variable sensitivity. In general a high spectral sensitivity was observed in 0.1–6 Gy range for the three film batches. For a given dose, no significant change in the spectra was observed with change in the dose rate. No significant dependency on the LET was observed for the EBT3 films irradiated with proton beams with dose-averaged LETs ranging from 1.14–6.50 keV µm−1 studied in this work. However, at a given dose, ~5% lower spectral response was observed in the films irradiated with protons compared to their counterparts irradiated with photon beams.

A linear relationship for the LET-dependence of Gafchromic EBT3 film in spot-scanning proton therapy

Radiochromic film (RCF) is a valuable dosimetric tool, primarily due to its sub-millimeter spatial resolution. For accurate proton dosimetry, the dependence of film response on linear energy transfer (LET) must be characterized and calibrated. In this work, we characterized film under-response, or ‘quenching’, as a function of dose-weighted linear energy transfer (LETd) in several proton fields and established a simple, linear relationship with LETd.We performed measurements as a function of depth in a PMMA phantom irradiated by a spot-scanning proton beam. The fields had energies of 71.3 MeV, 71.3 MeV with filter, and 159.9 MeV. At each depth (measurements taken in depth step sizes of 0.5–1 mm in the Bragg peak), we measured dose with a PTW Markus ion chamber and EBT3 RCF. EBT3 under-response was characterized by the ratio of dose measured with film to that with ion chamber. LETd values for our experimental setup were calculated using in-house clinical Monte Carlo code. Measured film under-response increased with LETd, from approximately 10% under-response for LETd = 5 keV µm−1 to approximately 20% for LETd = 8 keV µm−1. The under-response for all measurements was plotted versus LETd. A linear fit to the data was performed, yielding a function for under-response, , with respect to LETd: . Finally, the linear under-response relationship was applied to a film measurement within a spread-out Bragg peak (SOBP). Without correcting for LETd-dependence in the SOBP measurement, the discrepancy between film and Monte Carlo profiles was greater than 15% at the distal edge. With correction, the corrected film profile was within 2% and 1 mm of the Monte Carlo profile.RCF response depends on LETd, potentially under-responding by >15% in clinically-relevant scenarios. Therefore, it is insufficient to perform only a dose calibration; LET calibration is also necessary for accurate proton film dosimetry. The LETd-dependence of EBT3 can be described by a single, linear function over a range of clinically-relevant proton therapy LETd values.