Test of a pion range monitor using the radiative capture of pions on protonsπ −p→nγ

Summary The present paper demonstrates that neutron-photon pairs from radiative capture of stopped pions on chemically bound protons can be used to measure the range of negative pions within phantoms or a patient. Experimental results are given for a polyethylene and a water target of realistic size as well as for a Rando phantom. Monte-Carlo calculations were carried out in order to study the influence of various sizes of treatment volumes, detector geometries and neutron scattering within the targets upon the accuracy of the pion range determination. The results reveal clearly that a pion range monitor for the control of therapy plans and for actual patient irradiations can be designed according to the proposed principle. The absorbed dose required for a measurement is of the order of 0.1 Gy for a single pion beam if one aims at an accuracy of range determination of a few millimeters.     

Microdosimetry of diagnostic X rays: applications of the variance-covariance method.

Microdosimetric measurements in beams of diagnostic X rays (between 30 and 125 kV) have been performed. In these pulsed radiation fields, microdosimetric measurements are possible only by application of the variance-covariance technique. The dose mean lineal energy, yD, is determined for various simulated diameters, at different depths in the absorber, and at different points within the pulse intervals. From the measured temporal dependences one can also obtain values of yD for different X-ray pulse generators. The results demonstrate the potential of the variance-covariance method for a diversity of microdosimetric measurements in radiation protection and in the quality control of radiation beams.     

Energy deposition spectra of negative pions and their application to radiation therapy

Summary Treatment planning for pion radiation therapy must take into account changes in radiation quality within the patient. At the biomedical channelE3 of SIN (Swiss Institute for Nuclear Research) microdosimetric measurements have been performed to investigate radiation quality within pion irradiated phantoms. Results are presented in terms of microdosimetric spectra and derived quantities. As expected marked differences are observed between dose peak and plateau for narrow pion beams. The influence of simulated site diameter on measured spectra has been found to be more pronounced in the plateau region than in the peak. Investigation of the influence of peak width on radiation quality revealed a dilution of the high-LET dose fraction for broader peaks.     

Energy deposition spectra ofΠ − calculated from pion nucleus interaction data

Summary Distributions of absorbed dose in linear energy transfer (LET) and in lineal energy (y) are calculated for beams of negatively charged pions in a water phantom. The calculation is based on a comprehensive set of experimental data. The production of-ray electrons by fast particles is taken into account semiempirically. The results are compared with experimentally obtained spectra of ionization yields. The equivalence of data derived from pion nucleus interaction and taken from microdosimetry is clearly revealed. The distribution of absorbed dose is given in a sequence of contributions from the various secondary particles, i.e., the socalled star particles emitted following a nuclear capture process or the recoil nuclei from pion scatterings. This unique feature of calculated spectra will be useful for a characterization of the beam quality in view of the existing dependence of biological effects on track structure properties.     

Epithermal neutron beams for clinical studies of boron neutron capture therapy: a dosimetric comparison of seven beams

A comparison of seven epithermal neutron beams used in clinical studies of boron neutron capture therapy (BNCT) in Sweden (Studsvik), Finland (Espoo), Czech Republic (ReZ), The Netherlands (Petten) and the U.S. (Brookhaven and Cambridge) was performed to facilitate sharing of preclinical and clinical results. The physical performance of each beam was measured using a common dosimetry method under conditions pertinent to brain irradiations. Neutron fluence and absorbed dose measurements were performed with activation foils and paired ionization chambers on the central axis both in air and in an ellipsoidal water phantom. The overall quality of each beam was assessed by figures of merit determined from the total weighted dose profiles that assumed the presence of boron in tissue. The in-air specific beam contamination from both fast neutrons and gamma rays ranged between 8 and 65 x 10(-11) cGy(w) cm2 for the different beams and the epithermal neutron flux intensities available at the patient position differed by more than a factor of 20 from 0.2-4.3 x 10(9) n cm(-2) s(-1). Percentage depth dose profiles measured in-phantom for the individual photon, thermal and fast-neutron dose components differed only subtly in shape between facilities. Assuming uptake characteristics consistent with the currently used boronated phenylalanine, all the epithermal beams exhibit a useful penetration of 8 cm or greater that is sufficient to irradiate a lesion seated at the brain midline. The performance of the existing facilities will benefit from the introduction of advanced compounds through improved beam penetrability. This could increase by as much as 2 cm for the purest of beams, although the beam intensities generally need to be increased to between 2-5 x 10(9) n cm(-2) s(-1) to maintain manageable irradiation times. These data provide the first consistent measurement of beam performance at the different centers and will enable a preliminary normalization of the calculated patient dosimetry.     

Radiation quality of tritium beta-rays: microdosimetric distributions for nanometer-size targets in a medium containing tritiated water

To elucidate the characteristics of the action of tritium beta-rays, the following parameters are derived: electron slowing down spectra of primary electrons (beta-rays) and delta-rays in a medium containing tritiated water; and frequency distributions for the microdosimetric quantity j (number of effective primary events per track per target), fj, for nanometer-size targets exposed to tritiated water. Features of the radiation quality of tritium beta-rays are discussed by comparing the present results with those for 60Co gamma-rays and 7 MeV electrons. It is concluded that, although tritium beta-rays, 60Co gamma-rays, and 7 MeV electrons are classified as the same low l.e.t. radiation, the radiation quality of tritium beta-rays is considerably different from those of 60Co gamma-rays and 7 MeV electrons, and has specific features such as a high average l.e.t., a small total electron fluence per unit absorbed dose, and a different microdosimetric distribution, fj, for nanometer-size targets.     

Measuring output factors and beam profiles formed by multileaf collimators using Fricke gel dosimeter

The accuracy and precision are necessary factors in radiotherapy, especially for measurements involving output factors and beam profiles; in this case multileaf collimators (MLCs) and dosimeter systems are not employed to obtain an adequate absorbed dose. In this work, output factors and beam profiles using multileaf collimators were obtained through the Fricke Xylenol Gel (FXG) dosimeter irradiated with 6 MV photon beams. From the results, FXG dosimetry demonstrated to be an adequate dosimetric tool for radiotherapy applications using MLC.     

Effect of different stopping volumes of clinical pion beams at TRIUMF on the mouse small intestine

The survival of mouse jejunal crypt cells was measured using a microcolony assay following irradiation with one of three different pion stopping volumes. All treatments were done using the beam spot scanning system developed for clinical therapy at TRIUMF. Treatment volumes were Small, 10 ml of volume using 4 beam spots with a narrow stopping peak; Moderate, 40 ml of volume using 4 beam spots with an extended peak; Large, 1.2 liters of volume using 37 spots with an extended peak. The dose rate fluctuated considerably during treatment because of the scanning procedure. The relative biological effectiveness (RBE) values of pions were 1.11, 1.04, and 1.16 for the small, moderate, and large volumes, respectively. As the width of the stopping peak increased, from the narrow 4-cm peak of the small volume to the 12-cm peak of the moderate volume, the effectiveness of the pion beam decreased. This presumably reflects the low linear energy transfer contribution of the large number of passing pions in the wider stopping peak. The results indicate, however, a greater biological effectiveness for the large volume than for the moderate volume. Even though these fields had stopping peaks of similar width, the field size and dose rate were different. Although the increase in RBE may be partly due to an increased neutron flux from the larger volume, our results suggest that much of this apparent increase could be explained by differences in dose rate as a function of time for pions versus X rays.     

RBE of the MIT epithermal neutron beam for crypt cell regeneration in mice

The RBE of the new MIT fission converter epithermal neutron capture therapy (NCT) beam has been determined using intestinal crypt regeneration in mice as the reference biological system. Female BALB/c mice were positioned separately at depths of 2.5 and 9.7 cm in a Lucite phantom where the measured total absorbed dose rates were 0.45 and 0.17 Gy/ min, respectively, and irradiated to the whole body with no boron present. The gamma-ray (low-LET) contributions to the total absorbed dose (low- + high-LET dose components) were 77% (2.5 cm) and 90% (9.7 cm), respectively. Control irradiations were performed with the same batch of animals using 6 MV photons at a dose rate of 0.83 Gy/min as the reference radiation. The data were consistent with there being a single RBE for each NCT beam relative to the reference 6 MV photon beam. Fitting the data according to the LQ model, the RBEs of the NCT beams were estimated as 1.50 +/- 0.04 and 1.03 +/- 0.03 at depths of 2.5 and 9.7 cm, respectively. An alternative parameterization of the LQ model considering the proportion of the high- and low-LET dose components yielded RBE values at a survival level corresponding to 20 crypts (16.7%) of 5.2 +/- 0.6 and 4.0 +/- 0.7 for the high-LET component (neutrons) at 2.5 and 9.7 cm, respectively. The two estimates are significantly different (P = 0.016). There was also some evidence to suggest that the shapes of the curves do differ somewhat for the different radiation sources. These discrepancies could be ascribed to differences in the mechanism of action, to dose-rate effects, or, more likely, to differential sampling of a more complex dose-response relationship.     

Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment

PurposeTo determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.MethodsSimulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78–147 MeV and 177–223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.ResultsOut-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5–151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.ConclusionsThe agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.     

Piotron pion irradiation of cerebral capillaries in neonatal rats

Summary The microvasculature of the neonatal rat brain and its radiation-induced petechial hemorrhages were used as an in vivo model for studying the effect of negative pions on healthy normal tissue. By means of dose response curves (range: 2–6 gray) the RBE of peak pions with respect to 220 kVp X-rays was calculated. Whereas earlier studies involved irradiations with single beam pions (E3) of low dose rate (0.06–0.11 Gy per min) the present work was performed using pions of a multiport applicator (Piotron) of higher dose rate (1 Gy per min). The results obtained by Piotron pions agreed well with those obtained byE3 pions resulting in a RBE of 1.1. The difference between pion and X-rays, however, was statistically not significant. 0-(beta-hydroxyethyl)-rutosides known for their protective effect on radiation damage induced by either X-rays or electrons were used for evaluating any radioprotective effect on pion-induced damage of the microvasculature. They were applied subcutaneously in doses of 450 mg/kg body weight 30 min prior to irradiation. It could be demonstrated that the rutosides decreased the pion-induced radiation response significantly by a factor of 1.3.     

Chromatid breaks induced in Chinese hamster cells by low doses (12–100 rad) ofπ −-mesons

Summary Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G₂-phase of the cell cycle by ^–-mesons (6 rad/min peak-pion dose rate). Frequencies of induced single- and isochromatid breaks, acentric fragments and interchanges were compared with data obtained from 140 kV X-rays.The RBE-values were for the pion dose peak between 0.8–1.2 and for the pion dose plateau 0.5–0.9. Whereas for single chromatid breaks there was no significant difference between X-rays and peak pions for identical physical doses, the isochromatid breaks alone showed a significantly higher frequency for 100 rad peak pions.     

Microdosimetry of pulsed radiation fields employing the variance method

The relationship between dose mean lineal energy and relative variance has been exploited previously to derive yD from the calculated variance in current measurements in steady and uniform radiation fields. Recently Kellerer and Rossi made the observation that utilization of two detectors can make the variance technique practicable in time-varying fields. We report here the first measurements of yD for 10 MeV X rays and 9 and 18 MeV electrons from a pulsed linear accelerator using the variance method. Two independent analog-to-digital converters were used to obtain data from two spherical proportional counters in synchrony with the beam pulse. The method is described in detail and results are reported for site diameters of 1/2, 1, and 2 microns. Data for an accurate determination of yD can be obtained with this technique in less than 1 min, making possible an essentially "on line" determination of yD or zD in a clinical situation.     

Measured microdosimetric spectra and therapeutic potential of boron neutron capture enhancement of 252Cf brachytherapy

Californium-252 is a neutron-emitting radioisotope used as a brachytherapy source for radioresistant tumors. Presented here are microdosimetric spectra measured as a function of simulated site diameter and distance from applicator tube 252Cf sources. These spectra were measured using miniature tissue-equivalent proportional counters (TEPCs). An investigation of the clinical potential of boron neutron capture (BNC) enhancement of 252Cf brachytherapy is also provided. The absorbed dose from the BNC reaction was measured using a boron-loaded miniature TEPC. Measured neutron, photon and BNC absorbed dose components are provided as a function of distance from the source. In general, the absorbed dose results show good agreement with results from other measurement techniques. A concomitant boost to 252Cf brachytherapy may be provided through the use of the BNC reaction. The potential magnitude of this BNC enhancement increases with increasing distance from the source and is capable of providing a therapeutic gain greater than 30% at a distance of 5 cm from the source, assuming currently achievable boron concentrations.     

Influence of a shape of gold nanoparticles on the dose enhancement in the wide range of gold mass concentration for high-energy X-ray beams from a medical linac

AimThis work is focused on the Monte Carlo microdosimetric calculations taking into account the influence of the AuNPs’ shape, size and mass concentration on the radiation dose enhancement for the high-energy 6 MV and 18 MV X-ray therapeutic beams from a medical linac.BackgroundDue to a high atomic number and the photoelectric effect, gold nanoparticles can significantly enhance doses of ionizing radiation. However, this enhancement depends upon several parameters, such as, inter alia, nanoparticles’ shape etc.MethodThe simulated system was composed of the therapeutic beam, a water phantom with the target volume (with and without AuNPs) located at the depth of the maximum dose, i.e. at 1.5 cm for the 6 MV beam and at 3.5 cm for the 18 MV one. In the study the GEANT4 code was used because it makes it possible to get a very short step of simulation which is required in case of simulating the radiation interactions with nanostructures.ResultsThe dependence between the dose increase and the mass concentration of gold was determined and described by a simple mathematical formula for three different shapes of gold nanoparticles — two nanorods of different sizes and a flat 2D structure. The dose increase with the saturation occurring with the increasing mass concentration of gold was observed.ConclusionsIt was found that relatively large cylindrical gold nanoparticles can limit the increase of the dose absorbed in the target volume much more than the large 2D gold nanostructure.     

Derivation of radiation quality average parameters in neutron-gamma radiation fields with the high-pressure ionization chamber: theory and practice

The established radiation quality parameters in mixed neutron-gamma radiation fields may be measured by applying the initial (columnar) recombination of ions in tissue-equivalent (TE) high-pressure ionization chambers (recombination chambers). The mean quality factor can be determined to within 10-15% for mixed fields with neutrons ranging from thermal to 10 MeV, and the dose mean LET of the proton component can be determined to within 10-15% if the gamma-ray absorbed dose fraction is known. These average parameters are derived by measuring the ratio of the ionization currents collected at two high-field strengths and constant gas pressure applied to the ionization chamber. By utilizing approximate correlations between physical parameters in the neutron energy region from thermal to 10 MeV, the dose mean LET of the heavy ion component, the overall dose mean LET, and the microdosimetric parameter y0,D of the mixed field can also be derived. Experimental verification of the method is presented for various neutron-gamma radiation spectra in air and in water by comparison to theoretical calculations and results from low-pressure proportional counter measurements. Good agreement is shown. The TE high-pressure ionization chamber appears to have wide potential for use as a dose-equivalent meter in radiation protection or as a beam characterization device in radiobiology.     

Effect of different pion stopping volumes on the radiation response of mouse small intestine

This radiobiological investigation was based on measurements of crypt cell survival in mouse small intestine when the animals were exposed to 5 cm3 (spot), 350 cm3 and 3010 cm3 (the latter two were spot scans) pion stopping volumes generated by the multi-channel Piotron of the Swiss Institute for Nuclear Research. The experimental data obtained indicate that there was a decrease in biological effectiveness when the pion treatment volume was enlarged, irrespective of whether the pion dose was delivered in a single exposure or in four fractions. The r.b.e. values for pion beams relative to 200 kVp X-rays for the different experimental conditions used in this study are presented. The phenomenon of decreasing biological effectiveness with increasing pion stopping volume may be attributed to the following two factors: (1) when the pion stopping volume is increased there is a corresponding dilution of the high l.e.t. component of the beam; (2) the biological test system used may be sensitive to radiation dose rate which varied by a ratio of about 20 for the pion volumes used in this study.     

Dosimetric uncertainties impact on cell survival curve with low energy proton

There is an increasing number of radiobiological experiments being conducted with low energy protons (less than 5 MeV) for radiobiological studies due to availability of sub-millimetre focused beam. However, low energy proton has broad microdosimetric spectra which can introduce dosimetric uncertainty. In this work, we quantify the impact of this dosimetric uncertainties on the cell survival curve and how it affects the estimation of the alpha and beta parameters in the LQ formalism. Monte Carlo simulation is used to generate the microdosimetric spectra in a micrometer-sized water sphere under proton irradiation. This is modelled using radiobiological experiment set-up at the Centre of Ion Beam Application (CIBA) in National University of Singapore. Our results show that the microdosimetric spectra can introduce both systematic and random shifts in dose and cell survival; this effect is most pronounced with low energy protons. The alpha and beta uncertainties can be up to 10% and above 30%, respectively for low energy protons passing through thin cell target (about 10 microns). These uncertainties are non-negligible and show that care must be taken in using the cell survival curve and its derived parameters for radiobiological models.     

Measurements at theπE3 single beam correlated to dosimetry and therapy-planning for the pion applicator at SIN

Summary Using ionization chambers, aluminium activation, TLD and scintillation counters 3-dimensional total dose-distributions, stardose-distributions and pion stop-distributions have been measured in a single pion beam for various momenta and momentum spreads.It is demonstrated how these data will be used as an input into the therapy-planning program. The techniques developed are suited to check dynamical treatment with 60 pion beams.     

Preclinical Radiobiology with Pions: RBE — Values for Mouse Skin Damage as a Function of Single Doses of Pions

Summary The macroscopic reaction of the mouse skin was used to derive RBE values for negative-Mesons. Hind limbs of mice were irradiated with pions or X-rays. The pions were produced by the 590 MeV accelerator of the Schweizerisches Institut für Nuklearforschung (SIN). Early skin reaction was assessed over a period of 6–30 days after irradiation with single doses (20–45 Gy). The radiation damage was scored using an arbitrary scale of effect. The time pattern of development of the skin reaction and the subsequent healing after exposure both to pions and X-rays were similar, indicating that depletion and repopulation of the basal cells of the skin were comparable, both after pions and X-rays. RBE values as a function of pion doses at the peak (dose maximum), plateau and at the postpeak (12 mm downstream of the dose maximum) were computed with nonparametric statistical methods. The RBE at the peak and at the plateau relative to X-rays of the same dose rate was 1.15–1.25 and 0.85, respectively. The RBE of peak pions manifested a marked dependence on dose, when plateau pions were chosen as reference radiation. In this experiment there was no significant difference in RBE between peak and postpeak. The importance of some experimental condition (dose rate, irradiation volume) is discussed.Supported by the Swiss National Science Foundation (grant no. 3.682-0.75)