M. Pimpinella

Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum

The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed “bystander cells” neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo. Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks.

Charge collection efficiency in ionization chambers exposed to electron beams with high dose per pulse

The correction for charge recombination was determined for different plane-parallel ionization chambers exposed to clinical electron beams with low and high dose per pulse, respectively. The electron energy was nearly the same (about 7 and 9 MeV) for any of the beams used. Boags two-voltage analysis (TVA) was used to determine the correction for ion losses, k(s), relevant to each chamber considered. The presence of free electrons in the air of the chamber cavity was accounted for in determining k(s) by TVA. The determination of k(s) was made on the basis of the models for ion recombination proposed in past years by Boag, Hochhäuser and Balk to account for the presence of free electrons. The absorbed dose measurements in both low-dose-per-pulse (less than 0.3 mGy per pulse) and high-dose-per-pulse (20-120 mGy per pulse range) electron beams were compared with ferrous sulphate chemical dosimetry, a method independent of the dose per pulse. The results of the comparison support the conclusion that one of the models is more adequate to correct for ion recombination, even in high-dose-per-pulse conditions, provided that the fraction of free electrons is properly assessed. In this respect the drift velocity and the time constant for attachment of electrons in the air of the chamber cavity are rather critical parameters because of their dependence on chamber dimensions and operational conditions. Finally, a determination of the factor k(s) was also made by zero extrapolation of the 1/Q versus 1/V saturation curves, leading to the conclusion that this method does not provide consistent results in high-dose-per-pulse beams.

Characterization of a synthetic single crystal diamond Schottky diode for radiotherapy electron beam dosimetry

PURPOSE To investigate the dosimetric properties of synthetic single crystal diamond based Schottky diodes under irradiation with therapeutic electron beams from linear accelerators. METHODS A single crystal diamond detector was fabricated and tested under 6, 8, 10, 12, and 15 MeV electron beams. The detector performances were evaluated using three types of commercial detectors as reference dosimeters: an Advanced Markus plane parallel ionization chamber, a Semiflex cylindrical ionization chamber, and a p-type silicon detector. Preirradiation, linearity with dose, dose rate dependence, output factors, lateral field profiles, and percentage depth dose profiles were investigated and discussed. RESULTS During preirradiation the diamond detector signal shows a weak decrease within 0.7% with respect to the plateau value and a final signal stability of 0.1% (1σ) is observed after about 5 Gy. A good linear behavior of the detector response as a function of the delivered dose is observed with deviations below ±0.3% in the dose range from 0.02 to 10 Gy. In addition, the detector response is dose rate independent, with deviations below 0.3% in the investigated dose rate range from 0.17 to 5.45 Gy∕min. Percentage depth dose curves obtained from the diamond detector are in good agreement with the ones from the reference dosimeters. Lateral beam profile measurements show an overall good agreement among detectors, taking into account their respective geometrical features. The spatial resolution of solid state detectors is confirmed to be better than that of ionization chambers, being the one from the diamond detector comparable to that of the silicon diode. A good agreement within experimental uncertainties was also found in terms of output factor measurements between the diamond detector and reference dosimeters. CONCLUSIONS The observed dosimetric properties indicate that the tested diamond detector is a suitable candidate for clinical electron beam dosimetry.

Dosimetric characteristics of electron beams produced by a mobile accelerator for IORT

Energy and angular distributions of electron beams with different energies were simulated by Monte Carlo calculations. These beams were generated by the NOVAC7 system (Hitesys, Italy), a mobile electron accelerator specifically dedicated to intra-operative radiation therapy (IORT). The electron beam simulations were verified by comparing the measured dose distributions with the corresponding calculated distributions. As expected, a considerable difference was observed in the energy and angular distributions between the IORT beams studied in the present work and the electron beams produced by conventional accelerators for non-IORT applications. It was also found that significant differences exist between the IORT beams used in this work and other IORT beams with different collimation systems. For example, the contribution from the scattered electrons to the total dose was found to be up to 15% higher in the NOVAC7 beams. The water-to-air stopping power ratios of the IORT beams used in this work were calculated on the basis of the beam energy distributions obtained by the Monte Carlo simulations. These calculated stopping power ratios, s(w,air), were compared with the corresponding s(w,air) values recommended by the TRS-381 and TRS-398 IAEA dosimetry protocols in order to estimate the deviations between a dosimetry based on generic parameters and a dosimetry based on parameters specifically obtained for the actual IORT beams. The deviations in the s(w,air) values were found to be as large as up to about 1%. Therefore, we recommend that a preliminary analysis should always be made when dealing with IORT beams in order to assess to what extent the possible differences in the s(w,air) values have to be accounted for or may be neglected on the basis of the specific accuracy needed in clinical dosimetry.

CyberKnife beam output factor measurements: A multi-site and multi-detector study.

PURPOSE New promising detectors are available for measuring small field size output factors (OFs). This study focused on a multicenter evaluation of two new generation detectors for OF measurements on CyberKnife systems. METHODS PTW-60019 microDiamond and W1 plastic scintillation detector (PSD) were used to measure OFs on eight CyberKnife units of various generations for 5-60mm fixed cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes data corrected applying published Monte Carlo (MC) factors. PSD data were corrected for Čerenkov Light Ratio (CLR). The uncertainties related to CLR determination were estimated. RESULTS Considering OF values averaged over all centers, the differences between MC corrected diode and the other two detectors were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5mm and a trend inversion at 5mm with a difference of 0.2%. This behavior was consistent among the different units. OFs measured by PSD slightly under-responded compared to MC corrected diode for the smaller cones and the differences were within 1%. The observed CLR variability was 2.5% and the related variation in OF values was 1.9%. CONCLUSION This study indicates that CyberKnife microDiamond OF require corrections below 2%. The results are enhanced by the consistency observed among different units. Scintillator shows a good agreement to MC corrected diode but CLR determination remains critical requiring further investigations. The results emphasized the value of a multi-center validation over a single center approach.

Characteristics of the absorbed dose to water standard at ENEA.

The primary standard of absorbed dose to water established at ENEA for the Co-60 gamma-ray quality is based on a graphite calorimeter and an ionometric transfer system. This standard was recently improved after a more accurate assessment of some perturbation effects in the calorimeter and a modification of the water phantom shape and size. The conversion procedure requires two corresponding depths, one in graphite and one in water, where the radiation energy spectra must be the same. The energy spectra at the corresponding points were determined by a Monte Carlo simulation in water and graphite scaled phantoms. A thorough study of the calorimeter gap effect corrections was also made with regard to their dependence on depth and field size. A comparison between the ionization chamber calibration procedures based on the standards of absorbed dose to water and of air kerma was also made, confirming the consistency of the two methods.

Experimental determination of the beam quality dependence factors, kQ, for ionization chambers used in photon and electron dosimetry

Dosimetry in radiotherapy with ionization chambers calibrated in 60Co gamma beams in terms of absorbed dose to water, DW, can be performed if a factor conventionally denoted as kQ is known. The factor kQ depends on the beam quality and the chamber characteristics. Calculated values of the kQ factors for many types of ionization chamber have been recently published. In this work the experimental determination of the kQ factors for various ionization chambers was performed for 6 MV and 15 MV photon beams and for a 14 MeV electron beam. The kQ factors were determined by a procedure based on relative measurements performed with the ionization chamber and ferrous sulphate solution in 60Co gamma radiation and accelerator beams, respectively. The experimental kQ values are compared with the calculated values so far published. Theoretical and experimental kQ values are in fairly good agreement. The uncertainty in the experimental kQ factors determined in this work is less than about 1%, that is, appreciably smaller than the uncertainty of about 1.5% reported for the calculated values.

Multicenter evaluation of a synthetic single-crystal diamond detector for CyberKnife small field size output factors

PURPOSE The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference. METHODS Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers) and by Iris(™) variable aperture collimator (4 centers). Setup conditions were: 80cm source to detector distance, and 1.5cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements. RESULTS Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris(™) collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications. CONCLUSIONS Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris(™), demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size.

Correction factors for calibration of plane-parallel ionization chambers with a 60Co gamma-ray beam

The appropriate correction factors have been determined to enable plane-parallel ionization chambers to be calibrated using a 60Co photon beam with a known air kerma rate. These factors refer to different calibration conditions and to different types of plane-parallel chambers. The main purpose of these correction factors is to allow calibration procedures more widely practicable than those based on the use of an electron beam of sufficiently high energy. The condition required to apply the correction factors is that the characteristics of the chambers to be calibrated are the same as those reported for the chambers considered in the investigation. To this end the types of chambers investigated were among the most widely used plane-parallel chambers commercially available.

Small field output factors evaluation with a microDiamond detector over 30 Italian centers

PURPOSE The aim of the study was a multicenter evaluation of MLC&jaws-defined small field output factors (OF) for different linear accelerator manufacturers and for different beam energies using the latest synthetic single crystal diamond detector commercially available. The feasibility of providing an experimental OF data set, useful for on-site measurements validation, was also evaluated. METHODS This work was performed in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. The project was subdivided in two phases: in the first phase each center measured OFs using their own routine detector for nominal field sizes ranging from 10×10cm2 to 0.6×0.6cm2. In the second phase, the measurements were repeated in all centers using the PTW 60019 microDiamond detector. RESULTS The project enrolled 30 Italian centers. Micro-ion chambers and silicon diodes were used for OF measurements in 24 and 6 centers respectively. Gafchromic films and TLDs were used for very small field OFs in 3 and 1 centers. Regarding the measurements performed with the users detectors, OF standard deviations (SD) for field sizes down to 2×2cm2 were in all cases <2.7%. In the second phase, a reduction of around 50% of the SD was obtained using the microDiamond detector. CONCLUSIONS The measured values presented in this multicenter study provide a consistent dataset for OFs that could be a useful tool for improving dosimetric procedures in centers. The microDiamond data present a small variation among the centers confirming that this detector can contribute to improve overall accuracy in radiotherapy.