Use of alanine-silicone pellets for electron paramagnetic resonance gamma dosimetry.

Silicone is proposed as an alternative binding substance in the production of D-L alanine pellets used in electron paramagnetic resonance (EPR) dosimetry of gamma rays. The dosimeters are manufactured at room temperature, making the production simple. Examination by EPR silicone-alanine pellets irradiated with 60Co gamma rays in the dose range 10 to 10(6) Gy shows that the proposed silicone binder does not affect typical alanine dose-response curves. Thermal stability of the pellets below 40 degrees C is good, but their pre-dose EPR signal amplitude is slightly higher than for nonirradiated alanine.     

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams (“proton microchannels”) are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.     

Monte Carlo-based dose calculation engine for minibeam radiation therapy

Minibeam radiation therapy (MBRT) is an innovative radiotherapy approach based on the well-established tissue sparing effect of arrays of quasi-parallel micrometre-sized beams. In order to guide the preclinical trials in progress at the European Synchrotron Radiation Facility (ESRF), a Monte Carlo-based dose calculation engine has been developed and successfully benchmarked with experimental data in anthropomorphic phantoms. Additionally, a realistic example of treatment plan is presented. Despite the micron scale of the voxels used to tally dose distributions in MBRT, the combination of several efficiency optimisation methods allowed to achieve acceptable computation times for clinical settings (approximately 2 h). The calculation engine can be easily adapted with little or no programming effort to other synchrotron sources or for dose calculations in presence of contrast agents.     

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified.SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.     

Étude dosimétrique de préparations de médicaments radiopharmaceutiques au 68Ga

AimProduction of ⁶⁸Ga-radiopharmaceuticals is a rapidly growing field in France. However, operators may already be involved in other radiopharmaceutical activities. It is thus necessary to know the exposure of this new activity.Material and methodsFor passive dosimetry, a radiophotoluminescent (RPL) dosimeter, a thermoluminescent (TLD) chip, 2 TLD rings and a passive dosimeter for crystalline were used. For active dosimetry, an extremity dosimeter and a whole body dosimeter were used. This study was performed during semi-automatized production of ⁶⁸Ga-investigational medicinal products. Values were normalized to 500MBq manipulated (median activity using a 1850MBq ⁶⁸Ga-generator), 60 radiosynthesis (maximum enrollment ability of our center) and 2 operators. A LB123 proportional counter was used for quantification of external exposition to 10MBq ⁶⁸Ge and internal exposition by inhalation was theoretically assessed. ⁶⁸Ga emission attenuation by collective protection equipments was also discussed.ResultsConsidering passive dosimetry, the equivalent dose to extremities was 21.75 ± 0.34 mSv, the whole-body effective dose was 0.189 ± 0.011 mSv and the dose to crystalline was 0.925 ± 0.009 mSv. Considering active dosimetry, the equivalent dose to extremities was 8,75 ± 0.12 mSv and the whole-body effective dose was 0,088 ± 0.009 mSv. Total exposure to ⁶⁸Ge was 1.75 μSv.ConclusionIn our hands, ⁶⁸Ga is a directly transposable activity in radiopharmacies already equipped for ¹⁸F because of a dosimetry complying with regulatory limits and suitable radiation protection of collective equipments.     

Novel 6 MV X-ray photoneutron detection and dosimetry of medical accelerators

PurposeDosimetry of fast, epithermal and thermal photoneutrons in 6 MV X-ray beams of two medical accelerators were studied by novel dosimetry methods.MethodsA Siemens ONCOR and an Elekta COMPACT medical accelerators were used. Fast, epithermal and thermal photoneutron dose equivalents in 10 cm × 10 cm 6 MV X-rays fields were determined in air and on surface of a polyethylene phantom in X and Y directions. Polycarbonate dosimeters as bare or with enriched ¹⁰B convertors (with or without cadmium covers) were used applying a 50 Hz-HV electrochemical etching method.ResultsFast, epithermal and thermal photoneutron dose equivalents were efficiently determined respectively as ∼1145.8, ∼45.3 and ∼170.6 μSv in air and ∼1888.5, ∼96.1 and ∼640.6 μSv on phantom per 100 Gy X-rays at the isocenter of Siemens ONCOR accelerator in air. The dose equivalent is maximum at the isocenter which decreases as distance from it increases reaching a constant level. Tissue-to-air ratios are constants up to 15 cm from the isocenter. No photoneutrons was detected in the Elekta COMPACT accelerator.ConclusionsFast, epithermal and thermal photoneutron dosimetry of 6 MV X-rays were made by novel dosimetry methods in a Siemens ONCOR accelerator with sum dose equivalent per Gy of ∼0.0014% μSv with ∼0.21 MeV mean energy at the isocenter; i.e. ∼150 times smaller than that of 18 MV X-rays. This observation assures clinical safety of 6 MV X-rays in particular in single-mode machines like Elekta COMPACT producing no photoneutrons due to no “beryllium exit window” in the head structure.     

Feasibility study of the Fricke chemical dosimeter as an independent dosimetric system for the small animal radiation research platform (SARRP)

For the small animal radiation research platform (SARRP) with X-ray beams in the medium energy range (tube operating voltage at 220 kVp), reference dosimetry is based on the AAPM TG-61 recommendations following the in-phantom method. The objective of this study was to evaluate the feasibility of the Fricke solution as a dosimeter to determine the absorbed dose to water. Feasibility studies at this X-ray energy range are not widely available. We evaluated the accuracy, dose linearity and dose rate dependence in a comparison with an NE 2571 Farmer ionization chamber (IC) and measurements in water. The G(Fe³⁺) factor was calculated from the curve fitting of the chemical yields for two radioactive sources (¹⁹²Ir and ⁶⁰Co) and one X-ray system with a tube operating at 150 and 250 kVp. The same methodology was followed for the dependence of the G(Fe³⁺) value on the energy and the dose agreement assessment for 180 and 200 kVp in the SARRP. The Fricke system exhibits a good linear response over the range of 5–70 Gy and an accuracy better than 2% for a 2 Gy/min dose rate. The dose rate dependence is smaller than 1% for dose rates greater than 1 Gy/min. The dependence of the G(Fe³⁺) value on the energy is smaller than 0.41%, with dose agreements better than 2%. The feasibility of the dosimeter for measurements at high doses and high dose rates makes it a suitable tool for dosimetric verifications in several preclinical irradiation configurations.     

Simulation and measurement of microbeam dose distribution in lung tissue

Microbeam radiation therapy (MRT), a so far preclinical method in radiation oncology, modulates treatment doses on a micrometre scale. MRT uses treatment fields with a few ten micrometre wide high dose regions (peaks) separated by a few hundred micrometre wide low dose regions (valleys) and was shown to spare tissue much more effectively than conventional radiation therapy at similar tumour control rates. While preclinical research focused primarily on tumours of the central nervous system, recently also lung tumours have been suggested as a potential target for MRT.This study investigates the effect of the lung microstructure, comprising air cavities of a few hundred micrometre diameter, on the microbeam dose distribution in lung. In Monte Carlo simulations different models of heterogeneous lung tissue are compared with pure water and homogeneous air–water mixtures. Experimentally, microbeam dose distributions in porous foam material with cavity sizes similar to the size of lung alveoli were measured with film dosimetry at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France.Simulations and experiments show that the microstructure of the lung has a huge impact on the local doses in the microbeam fields. Locally, material inhomogeneities may change the dose by a factor of 1.7, and also average peak and valley doses substantially differ from those in homogeneous material.Our results imply that accurate dose prediction for MRT in lung requires adequate models of the lung microstructure. Even if only average peak and valley doses are of interest, the assumption of a simple homogeneous air–water mixture is not sufficient. Since anatomic information on a micrometre scale are unavailable for clinical treatment planning, alternative methods and models have to be developed.     

Dosimetric investigation of a new high dose rate 192Ir brachytherapy source,IRAsource, by Monte Carlo method

PurposeThe purpose of the present study was to perform an independent calculation of dosimetric parameters associated with a new ¹⁹²Ir brachytherapy source model, IRAsource.Materials and methodsThe parameters of air kerma strength (AKS), dose rate constant (DRC), geometry function (GF), radial dose function (RDF), as well as two-dimensional (2D) anisotropy function (AF) of IRAsource ¹⁹²Ir source model were calculated in this study. The MC n-particle extended (MCNPX) code was also employed for simulating high dose rate (HDR), IRAsource and ¹⁹²Ir source; and formalism was used for calculating dosimetry parameters based on task group number 43 updated report (TG-43 U1).ResultsThe results of this study were consistent with the ones reported about the IRAsource source by Sarabiasl et al. The AKS per 1 mCi activity and the DRC values were also equal to 3.65 cGycm² h^–1 mCi^–1 and 1.094 cGyh^–1U^–1; respectively. The comparison of the results of the DRC and the RDF reported by Sarabiasl et al. also validated the ¹⁹²Ir IRAsource simulation in this study. Moreover, the AFs of IRAsource source model were in a good agreement with those of Sarabiasl et al. at different distances, which could be attributed to identical geometries.ConclusionIn line with those reported by Sarabiasl et al., the results of this study confirmed the IRAsource ¹⁹²Ir source for clinical uses. The calculated dosimetric parameters of the IRAsource source could be utilized in clinical practices as input data sets or for validation of treatment planning system calculations.     

Effect of verification imaging on in vivo dosimetry results using Gafchromic EBT3 film

In this work, the apparent treatment dose that kV planar or CBCT imaging contributes to Gafchromic EBT3 film used for in vivo dosimetry, was investigated. Gafchromic EBT3 film pieces were attached to a variety of phantoms and irradiated using the linear accelerator’s built-in kV imaging system, in both kV planar mode and CBCT mode. To evaluate the sensitivity of the film in the clinical scenario where dose contributions are received from both imaging and treatment, additional pieces of film were irradiated using base doses of 50 cGy and then irradiated using selected kV planar and CBCT techniques. For kV planar imaging, apparent treatment doses of up to 3.4 cGy per image pair were seen. For CBCT, apparent treatment doses ranged from 0.22 cGy to 3.78 cGy. These apparent doses were reproducible with and without the inclusion of the 50 cGy base dose. The contribution of apparent treatment dose from both planar kV as well as CBCT imaging can be detected, even in conjunction with an actual treatment dose. The magnitude of the apparent dose was found to be dependent on patient geometry, scanning protocol, and measurement location. It was found that the apparent treatment dose from the imaging could add up to 8% of additional uncertainty to the in vivo dosimetry result, if not taken into account. It is possible for this apparent treatment dose to be accounted for by subtraction of the experimentally determined apparent doses from in vivo measurements, as demonstrated in this work.     

The European Joint Research Project UHDpulse – Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates

UHDpulse – Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.     

A new EPR dosimeter based on glutamic acid for radiation processing application

Radiation and Environmental Biophysics - l-Glutamic acid (L-GA) pellets (3.8 mm × 4 mm) and powder dosimeters were studied in the dose range of...     

Electron radiotherapy (IOERT) for applications outside of the breast: Dosimetry and influence of tissue inhomogeneities

PurposeThe purpose of study is to investigate the dosimetry of electron intraoperative radiotherapy (IOERT) of the Intraop Mobetron 2000 mobile LINAC in treatments outside of the breast. After commissioning and external validation of dosimetry, we report in vivo results of measurements for treatments outside the breast in a large patient cohort, and investigate if the presence of inhomogeneities can affect in vivo measurements.Methods and materialsApplicator factors and profile curves were measured with a stereotactic diode. The applicators factors of the 6 cm flat and beveled applicators were also confirmed with radiochromic films, parallel-plate ion chamber and by an external audit performed with ThermoLuminescent Dosimeters (TLDs). The influence of bone on dose was investigated by using radiochromic films attached to an insert equivalent to cortical bone, immersed in the water phantom. In vivo dosimetry was performed on 126 patients treated with IOERT using metal oxide-silicon semiconductor field effect transistors (MOSFETs) placed on the tumor bed.ResultsRelatively small differences were found among different detectors for measurements of applicator factors. In the external audit, the agreement with the TLD was mostly within ±0.2%. The largest increase of dose due to the presence of cortical bone insert was +6.0% with energy 12 MeV and 3 cm applicator. On average, in vivo dose was significantly (+3.1%) larger than prescribed dose.ConclusionIOERT in applications outside the breast results in low discrepancies between in vivo and prescribed doses, which can be also explained with the presence of tissue inhomogeneity.     

Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications

PurposeTo investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in ¹⁹²Ir interstitial breast brachytherapy.Materials and methodsA 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters.ResultsTG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities.ConclusionWhile TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence.     

Quantitative comparison between the commercial software STRATOS® by Philips and a homemade software for voxel-dosimetry in radiopeptide therapy

BackgroundTargeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS.MethodsThe validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of ¹⁷⁷Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study.ResultsIn phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of 5%, but with a remarkable range (−40%, +60%) between the two software packages. Voxel-dosimetry allows to estimate the dose non-homogeneities in volumes, which may be evaluated through DVHs.ConclusionThis study demonstrates that a fully 3D voxel-dosimetry with multiple SPECT images is feasible by using home-made or commercial software package and absorbed dose results obtained are similar. The main difference between the studied tools was observed in the activity integration method (effective vs physical half-time to time activity curve tail). We believe that an effective half-time integration method produces a more accurate approximation of clinical uptake and resultant dosimetry.     

Proton microbeam radiotherapy with scanned pencil-beams – Monte Carlo simulations

Irradiation, delivered by a synchrotron facility, using a set of highly collimated, narrow and parallel photon beams spaced by 1 mm or less, has been termed Microbeam Radiation Therapy (MRT). The tolerance of healthy tissue after MRT was found to be better than after standard broad X-ray beams, together with a more pronounced response of malignant tissue. The microbeam spacing and transverse peak-to-valley dose ratio (PVDR) are considered to be relevant biological MRT parameters. We investigated the MRT concept for proton microbeams, where we expected different depth-dose profiles and PVDR dependences, resulting in skin sparing and homogeneous dose distributions at larger beam depths, due to differences between interactions of proton and photon beams in tissue. Using the FLUKA Monte Carlo code we simulated PVDR distributions for differently spaced 0.1 mm (sigma) pencil-beams of entrance energies 60, 80, 100 and 120 MeV irradiating a cylindrical water phantom with and without a bone layer, representing human head. We calculated PVDR distributions and evaluated uniformity of target irradiation at distal beam ranges of 60–120 MeV microbeams. We also calculated PVDR distributions for a 60 MeV spread-out Bragg peak microbeam configuration. Application of optimised proton MRT in terms of spot size, pencil-beam distribution, entrance beam energy, multiport irradiation, combined with relevant radiobiological investigations, could pave the way for hypofractionation scenarios where tissue sparing at the entrance, better malignant tissue response and better dose conformity of target volume irradiation could be achieved, compared with present proton beam radiotherapy configurations.     

Calculation of tumour and normal tissue biological effective dose in 90Y liver radioembolization with different dosimetric methods

PurposeRadioembolization with ⁹⁰Y microspheres is an effective treatment for unresectable liver tumours. Two types of microspheres are available: resin (SIR-Spheres®) and glass (Theraspheres®). The aim of this study is to compare biological effective dose (BED) values obtained with three different dosimetric methods.Methods29 HCC patients were included in this study: 15 were treated with resin(mean injected activity 1.5 GBq, range 0.8–2.7 GBq) and 14 with glass microspheres (2.6 GBq, range 1.3–4.1 GBq). Average doses to tumours and normal liver tissues were calculated with AAPM, multi-compartmental MIRD and Voxel-based methods and consequently the BED values were obtained. Planar images were used for the AAPM method: ^99mTc-MAA SPECT-CT attenuation and scatter corrected images (resin) and ⁹⁹m Tc-MAA SPECT attenuation corrected (glass) were employed for the other two methods.ResultsRegardless of type of microspheres, both for tumours and normal liver tissues, no significant statistical differences were found between MIRD and Voxel for both doses and BED values. Conversely AAPM gave discordant results with respect to the other two methods (Mann-Whitney p-values ⩽ 0.01). For resin spheres the calculated tumour-to-normal tissue ratios on planar images were on average 14 times greater than those obtained on SPECT-CT images, while they were 4 times greater on glass. A linear correlation was observed between MIRD and Voxel BEDs.ConclusionsThe AAPM method appears to be less precise for absorbed dose and BED estimation, while MIRD and voxel based dosimetry are more confident each other.     

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy

PurposeTo characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator.MethodsThe dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.).The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors.ResultsA good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under ⁶⁰Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R₅₀ values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes.ConclusionsThe microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions.