Optimized beam shaping assembly for a 2.1-MeV proton-accelerator-based neutron source for boron neutron capture therapy.

Boron Neutron Capture Therapy (BNCT) is facing a new era where different projects based on accelerators instead of reactors are under development. The new facilities can be placed at hospitals and will increase the number of clinical trials. The therapeutic effect of BNCT can be improved if a optimized epithermal neutron spectrum is obtained, for which the beam shape assembly is a key ingredient. In this paper we propose an optimal beam shaping assembly suited for an affordable low energy accelerator. The beam obtained with the device proposed accomplishes all the IAEA recommendations for proton energies between 2.0 and 2.1 MeV. In addition, there is an overall improvement of the figures of merit with respect to BNCT facilities and previous proposals of new accelerator-based facilities.

The E LiBANS project: Thermal and epithermal neutron sources based on a medical Linac.

The E_LIBANS project (INFN) aims at producing neutron facilities for interdisciplinary irradiation purposes among which pre-clinical research for BNCT. After the successful setting-up of the thermal neutron source based on a medical LINAC, a similar apparatus for epithermal neutrons has been developed. Both structures are based on an Elekta 18 MV coupled with a photoconverter-moderator system which deploys the (γ,n) reaction to convert the X-rays into neutrons. This communication describes the two neutron sources and the results obtained in their characterization.

A systematic review of clinical applications of polymer gel dosimeters in radiotherapy.

Radiotherapy has rapidly improved because of the use of new equipment and techniques. Hence, the appeal for a feasible and accurate three-dimensional (3D) dosimetry system has increased. In this regard, gel dosimetry systems are accurate 3D dosimeters with high resolution. This systematic review evaluates the clinical applications of polymer gel dosimeters in radiotherapy. To find the clinical applications of polymer gel dosimeters in radiotherapy, a full systematic literature search was performed on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in electronic databases up to January 31, 2017, with use of search-related terms in the titles and abstracts of articles. A total of 765 articles were screened in accordance with our inclusion and exclusion criteria. Eventually, 53 articles were included in the study. The findings show that most clinical applications of polymer gel dosimeters relate to external radiotherapy. Most of the gel dosimeters studied have acceptable dose accuracy as a 3D dosimeter with high resolution. It is difficult to judge which is the best polymer gel dosimeter to use in a clinical setting, because each gel dosimeter has advantages and limitations. For example, methacrylic acid-based gel dosimeters have high dose sensitivity and low toxicity, while their dose response is beam energy dependent; in contrast, N-isopropylacrylamide gel dosimeters have low dose resolution, but their sensitivity is lower and they are relatively toxic.

Monte Carlo simulation-based design for an electron-linear-accelerator-driven subcritical neutron multiplier for boron neutron capture therapy.

Fuel configurations for a subcritical neutron multiplier, which was embedded in a beam-shaping assembly and irradiated by electrons from a linear accelerator, were examined to maximize the production of the epithermal neutron flux for boron neutron capture therapy. The epithermal neutron flux at the treatment position increased as the area per uranium fuel plate increased and was estimated to be 2 × 109 cm-2 s-1 when the subcritical neutron multiplier was irradiated by a 4.4 kW (0.22 mA) beam of 20 MeV electrons.

Investigation of the neutron spectrum measurement method for dose evaluation in boron neutron capture therapy.

In boron neutron capture therapy, it is important to evaluate the dose administered to a patient's body outside the tumour area. The exposure dose is evaluated by calculation; however, the calculated value must be validated using a measured value. The dose evaluations based on the measured neutron spectrum are investigated. Multi-foil activation, combined with a LiCaAlF6 scintillation detector and an imaging plate, is proposed as a measurement method. The proposed method can measure the neutron spectrum at various points quickly.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor.

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam. To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7Li(p,n)7Be neutron production reaction is proposed. To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered. In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38. All of these calculations were carried out using the Monte Carlo MCNP code.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT.

Analysis of MCNP simulated gamma spectra of CdTe detectors for boron neutron capture therapy.

The next step in the boron neutron capture therapy (BNCT) is the real time imaging of the boron concentration in healthy and tumor tissue. Monte Carlo simulations are employed to predict the detector response required to realize single-photon emission computed tomography in BNCT, but have failed to correctly resemble measured data for cadmium telluride detectors. In this study we have tested the gamma production cross-section data tables of commonly used libraries in the Monte Carlo code MCNP in comparison to measurements. The cross section data table TENDL-2008-ACE is reproducing measured data best, whilst the commonly used ENDL92 and other studied libraries do not include correct tables for the gamma production from the cadmium neutron capture reaction that is occurring inside the detector. Furthermore, we have discussed the size of the annihilation peaks of spectra obtained by cadmium telluride and germanium detectors.

Optimization of the Compton camera for measuring prompt gamma rays in boron neutron capture therapy.

Optimization of the Compton camera for measuring prompt gamma rays (0.478MeV) emitted during boron neutron capture therapy (BNCT) was performed with Geant4. The parameters of the Compton camera were determined as follows: 3cm thick - 10cm wide scatter detector (Silicon), 10cm thick - 10cm wide absorber detector (Germanium), and 1cm distance between the scatter and absorber detectors. For a typical brain tumor treatment, the overall detection efficiency of the optimized Compton camera was approximately 0.1425% using the Snyder's head phantom with a sphere tumor (4cm diameter and ~1cm depth).

Simulation study of accelerator based quasi-mono-energetic epithermal neutron beams for BNCT.

Filtered neutron techniques were applied to produce quasi-mono-energetic neutron beams in the energy range of 1.5-7.5 keV at the accelerator port using the generated neutron spectrum from a Li (p, n) Be reaction. A simulation study was performed to characterize the filter components and transmitted beam lines. The feature of the filtered beams is detailed in terms of optimal thickness of the primary and additive components. A computer code named "QMNB-AS" was developed to carry out the required calculations. The filtered neutron beams had high purity and intensity with low contamination from the accompanying thermal, fast neutrons and γ-rays.

Capability of NIPAM polymer gel in recording dose from the interaction of (10)B and thermal neutron in BNCT.

The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT.

A study on the optimum fast neutron flux for boron neutron capture therapy of deep-seated tumors.

High-energy neutrons, named fast neutrons which have a number of undesirable biological effects on tissue, are a challenging problem in beam designing for Boron Neutron Capture Therapy, BNCT. In spite of this fact, there is not a widely accepted criterion to guide the beam designer to determine the appropriate contribution of fast neutrons in the spectrum. Although a number of researchers have proposed a target value for the ratio of fast neutron flux to epithermal neutron flux, it can be shown that this criterion may not provide the optimum treatment condition. This simulation study deals with the determination of the optimum contribution of fast neutron flux in the beam for BNCT of deep-seated tumors. Since the dose due to these high-energy neutrons damages shallow tissues, delivered dose to skin is considered as a measure for determining the acceptability of the designed beam. To serve this purpose, various beam shaping assemblies that result in different contribution of fast neutron flux are designed. The performances of the neutron beams corresponding to such configurations are assessed in a simulated head phantom. It is shown that the previously used criterion, which suggests a limit value for the contribution of fast neutrons in beam, does not necessarily provide the optimum condition. Accordingly, it is important to specify other complementary limits considering the energy of fast neutrons. By analyzing various neutron spectra, two limits on fast neutron flux are proposed and their validity is investigated. The results show that considering these limits together with the widely accepted IAEA criteria makes it possible to have a more realistic assessment of sufficiency of the designed beam. Satisfying these criteria not only leads to reduction of delivered dose to skin, but also increases the advantage depth in tissue and delivered dose to tumor during the treatment time. The Monte Carlo Code, MCNP-X, is used to perform these simulations.

Optimization of the beam shaping assembly in the D-D neutron generators-based BNCT using the response matrix method.

Optimization of the Beam Shaping Assembly (BSA) has been performed using the MCNP4C Monte Carlo code to shape the 2.45 MeV neutrons that are produced in the D-D neutron generator. Optimal design of the BSA has been chosen by considering in-air figures of merit (FOM) which consists of 70 cm Fluental as a moderator, 30 cm Pb as a reflector, 2mm (6)Li as a thermal neutron filter and 2mm Pb as a gamma filter. The neutron beam can be evaluated by in-phantom parameters, from which therapeutic gain can be derived. Direct evaluation of both set of FOMs (in-air and in-phantom) is very time consuming. In this paper a Response Matrix (RM) method has been suggested to reduce the computing time. This method is based on considering the neutron spectrum at the beam exit and calculating contribution of various dose components in phantom to calculate the Response Matrix. Results show good agreement between direct calculation and the RM method.

A feasibility study of the post-irradiation dose estimation with SPECT technique for BNCT.

Various radioactive nuclei are generated in and around the target volume after the irradiation for boron neutron capture therapy. By measuring and estimating the distributions of these nuclei with the technique of single photon emission computed tomography (SPECT), more accurate post-irradiation dose-estimation can be expected. The feasibility study was performed mainly by simulation. The radioactivity densities for Cl-38, Ca-49 and Na-24 just after the irradiation were calculated to be 100-1000 Bq/cm(3) in and around the target volume. It was confirmed that these nuclei could be detected by SPECT under some conditions. Using the density differences for these generated nuclei, discrimination between soft-tissue area and bone area can be achieved. In focusing on the shallower 1cm(3) voxel, the necessary counting-time for Na-24 was estimated to be a few tens of minutes when the distance between the SPECT detector and the voxel was shortened to 6 cm.

Dosimetric evaluation of neutron capture therapy for local advanced breast cancer.

Local recurrence breast cancer is one of the most difficult conditions to cure and there is a need for new therapy. If sufficient boron compound can be targeted to the tumor, boron neutron capture therapy (BNCT) can be applied to local recurrent breast cancer. In this study, we performed a preliminary dosimetry with a phantom model of the mammary gland at Kyoto University Research Reactor (KUR), and a feasibility dosimetry with JAERI Computational Dosimetry System (JCDS) at JRR4 reactor of Japan Atomic Research Institute. We performed preliminary dosimetry of a phantom model of the mammary gland with thermal neutron irradiation (OO-0011 mode) on LiF collimation at KUR. The thermal neutron flux was 5.16 E+08 cm(-2)s(-1) at the surface of phantom. The blood boron concentration is estimated to be 30 ppm; tumor boron concentration is also estimated to be 90 ppm according to tumor/blood ratio 3 and skin/blood ratio 1.2. Tumor RBE dose is estimated to be 47 Gy/h, and skin RBE dose is 12.4 Gy/h. In case of advanced breast cancer, we performed the feasibility estimation of 3D construction of tumor according to the MRI imaging of a patient with epithermal neutron mode at JRR4. The blood boron concentration (ppm) and tumor/normal tissue ratio are estimated to be 24 and 3.5, respectively. Skin RBE dose is restricted to 10 Gy/h, the maximum tumor RBE dose, minimum tumor RBE dose, and mean tumor RBE dose are 42.2, 11.3, and 28.9 Gy-Eq, respectively, in half hour irradiation. In this study, we showed the possibility to apply BNCT to local recurrent breast cancer. We can irradiate tumors selectively and as safely as possible, reducing the effects on neighboring healthy tissues.

The study of physics and thermal characteristics for in-hospital neutron irradiator (IHNI).

The IHNI is designed for boron neutron capture therapy (BNCT) based on miniature neutron source reactor (MNSR). The reactor with thermal power 30 kW is an undermoderated reactor of pool-tank type, and UO(2) as fuel, light water as coolant and moderator, and metallic beryllium as reflector. The fission heat produced by the reactor is removed by the natural convection. The paper gives the calculating results of critical mass and the worths of central control rod, auxiliary control rod, reactivity regulator and neutron beam equipments. The parameters at thermal and small thermal ports and at epithermal port were calculated by optimizing combination of kinds of material by MCNP code. The dynamic feature research was done by RELAP5 code when the reactivities of 3, 4.5 and 6 mK were inserted, respectively. The results show that the reactor power can be limited to safe level by itself owing to the Doppler effect of fuel element and moderator negative temperature effect when the 6 mK reactivity was inserted into the reactor.

Building of scientific information system for sustainable development of BNCT in Bulgaria.

Building a boron neutron capture therapy (BNCT) facility is foreseen within the reconstruction of the Research Reactor IRT (IRT) of the Institute for Nuclear Research and Nuclear Energy of the Bulgaria Academy of Sciences (INRNE). The development of BNCT at IRT plays a very significant role in the plan for sustainable application of the reactor. A centralized scientific information system on BNCT is being built at the INRNE with the purpose to collect and sort new information as knowledge accumulated during more than thirty years history of BNCT. This BNCT information system will help the creation and consolidation of a well informed and interconnected interdisciplinary team of physicists, chemists, biologists, and radio-oncologists for establishing BNCT cancer treatment in Bulgaria. It will strengthen more intensive development of the national network as well as its enlargement to the Balkan region countries. Furthermore, to acquaint the public at large with the opportunity for BNCT cancer treatment will be addressed. Human, social, and economics results due to BNCT for many patients from Balkan region are expected.

Preliminary modeling of BNCT beam tube on IRT in Sofia.

The technical design of the research reactor IRT in Sofia is in progress. It includes an arrangement for a BNCT facility for tumor treatment. Modeling of geometry and material composition of filter/collimator for the BNCT beam tube on IRT has been carried out following the beam tube configuration of the Massachusetts Institute of Technology Reactor [Harling et al., 2002. The fission converter-based epithermal neutron irradiation facility at the Massachusetts Institute of Technology Reactor. Nucl. Sci. Eng. 140, 223-240.] and taking into account an ability to include the tube into the IRT reactor geometry. The results of neutron and gamma transport calculations performed for the model have shown that the facility will be able to supply an epithermal neutron flux of about 5 x 10(9) n cm(-2)s(-1), with low contamination from fast neutrons and gamma rays that would be among the best facilities currently available. An optimiziation study has been performed for the beam collimator, following similar studies for the TAPIRO research reactor in Italy. [Nava et al., 2005. Monte Carlo optimization of a BNCT facility for treating brain gliomas at the TAPIRO reactor. Radiat. Prot. Dosim. 116 (1-4), 475-481.].

In vitro neutron irradiation of glioma and endothelial cultured cells.

To fully develop its potential boron neutron capture therapy (BNCT) requires the combination of a suitable thermal/epithermal neutron flux together with a selective intake of (10)B-boron nuclei in the target tissue. The latter condition is the most critical to be realized as none of the boron carriers used for experimental or clinical purposes proved at the moment an optimal selectivity for cancer cells compared to normal cells. In addition to complex physical factors, the assessment of the intracellular concentration of boron represent a crucial parameter to predict the dose delivered to the cancer cells during the treatment. Nowadays the dosimetry calculation and then the prediction of the treatment effectiveness are made using Monte Carlo simulations, but some of the model assumption are still uncertain: the radiobiological dose efficacy and the probability of tumour cell survival are crucial parameters that needs a more reliable experimental approach. The aim of this work was to evaluate the differential ability of two cell lines to selectively concentrate the boron-10 administered as di-hydroxyboryl-phenylalanine (BPA)-fructose adduct, and the effect of the differential boron intake on the damage produced by the irradiation with thermal neutrons; the two cell lines were selected to be representative one of normal tissues involved in the active/passive transport of boron carriers, and one of the tumour. Recent in vitro studies demonstrated how BPA is taken by proliferating cells, however the mechanism of BPA uptake and the parameters driving the kinetics of influx and the elimination of BPA are still not clarified. In these preliminary studies we analysed the survival of F98 and human umbilical vein endothelial cells (HUVEC) cells line after irradiation, using different thermal fluencies at the same level of density population and boron concentration in the growing medium prior the irradiation. This is first study performed on endothelium model obtained by a primary human cell line (HUVEC). The perspective application of this work is to develop a model able to foresee the effects produced by different combination of boron influx with a thermal neutron fluencies, applying a standardized radiobiological methodology, and in particular to continue the investigation of the radiobiological effects on the endothelium model as the main tissue involved in the transport of boronated molecules.

Spectral performance of a composite single-crystal filtered thermal neutron beam for BNCT research at the University of Missouri.

Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The calculated and measured thermal neutron fluxes produced at the irradiation location are 9.6 x 10(8) and 8.8 x 10(8)neutrons/cm(2)s, respectively. Calculated and measured cadmium ratios (Au foils) are 217 and 132. These results indicate a well-thermalized neutron spectrum with sufficient thermal neutron flux for a variety of small animal BNCT studies.