A toolkit for epithermal neutron beam characterisation in BNCT

Methods for dosimetry of epithermal neutron beams used in boron neutron capture therapy (BNCT) have been developed and utilised within the Finnish BNCT project as well as within a European project for a code of practise for the dosimetry of BNCT. One outcome has been a travelling toolkit for BNCT dosimetry. It consists of activation detectors and ionisation chambers. The free-beam neutron spectrum is measured with a set of activation foils of different isotopes irradiated both in a Cd-capsule and without it. Neutron flux (thermal and epithermal) distribution in phantoms is measured using activation of Mn and Au foils, and Cu wire. Ionisation chamber (IC) measurements are performed both in-free-beam and in-phantom for determination of the neutron and gamma dose components. This toolkit has also been used at other BNCT facilities in Europe, the USA, Argentina and Japan.     

Application of TEPC microdosimetry to boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a bimodal radiation therapy used primarily for highly malignant gliomas. Tissue-equivalent proportional counter (TEPC) microdosimetry has proven an ideal dosimetry technique for BNCT, facilitating accurate separation of the photon and neutron absorbed dose components, assessment of radiation quality and measurement of the BNC dose. A miniature dual-TEPC system has been constructed to facilitate microdosimetry measurements with excellent spatial resolution in high-flux clinical neutron capture therapy beams. A 10B-loaded TEPC allows direct measurement of the secondary charged particle spectrum resulting from the BNC reaction. A matching TEPC fabricated from brain-tissue-equivalent plastic allows evaluation of secondary charged particle spectra from photon and neutron interactions in normal brain tissue. Microdosimetric measurements performed in clinical BNCT beams using these novel miniature TEPCs are presented, and the advantages of this technique for such applications are discussed.     

BNCT医院中子照射器辐射场特性参数初步测量

为验证BNCT医院中子照射器的设计效果,对其辐射场的特性参数如中子能谱、中子通量密度及其空间分布、中子和γ吸收剂量率及其空间分布等进行了测量。针对该照射器的特点,建立了一套由多球谱仪、235U裂变电离室、金箔、组织等效正比计数器和热释光探测器组成的测量系统,利用蒙特卡洛计算方法优化设计探测器的结构,以提高超热能区的分辨率和甄别不同能量成分中子的能力。初步测量结果表明,该照射器的中子通量密度达到了预期设计要求。     

Microdosimetric evaluation of the neutron field for BNCT at Kyoto University reactor by using the PHITS code

In this study, microdosimetric energy distributions of secondary charged particles from the (10)B(n,α)(7)Li reaction in boron-neutron capture therapy (BNCT) field were calculated using the Particle and Heavy Ion Transport code System (PHITS). The PHITS simulation was performed to reproduce the geometrical set-up of an experiment that measured the microdosimetric energy distributions at the Kyoto University Reactor where two types of tissue-equivalent proportional counters were used, one with A-150 wall alone and another with a 50-ppm-boron-loaded A-150 wall. It was found that the PHITS code is a useful tool for the simulation of the energy deposited in tissue in BNCT based on the comparisons with experimental results.     

Characterisation of the TAPIRO BNCT epithermal facility

A collimated epithermal beam for boron neutron capture therapy (BNCT) research has been designed and built at the TAPIRO fast research reactor. A complete experimental characterisation of the radiation field in the irradiation chamber has been performed, to verify agreement with IAEA requirements. Slow neutron fluxes have been measured by means of an activation technique and with thermoluminescent detectors (TLDs). The fast neutron dose has been determined with gel dosemeters, while the fast neutron spectrum has been acquired by means of a neutron spectrometer based on superheated drop detectors. The gamma-dose has been measured with gel dosemeters and TLDs. For an independent verification of the experimental results, fluxes, doses and neutron spectra have been calculated with Monte Carlo simulations using the codes MCNP4B and MCNPX_2.1.5 with the direct statistical approach (DSA). The results obtained confirm that the epithermal beams achievable at TAPIRO are of suitable quality for BNCT purposes.     

Stability of A-150 plastic ionisation chamber response over a approximately 30-y period

At the Northern Illinois University Institute for Neutron Therapy at Fermilab, the clinical tissue-equivalent ionisation chamber response is measured every treatment day using a cesium source that was configured to match readings obtained at the National Bureau of Standards. Daily measurements are performed in air using the air-to-tissue dose conversion factors given in AAPM Report #7. The measured exposure calibration factors have been tabulated and graphed as a function of time from 1978 to present. For A-150 plastic ionisation chambers, these factors exhibit a sinusoidal variation with a period of approximately 1 y and amplitude of +/- 1%. This variation, attributable to the hygroscopic nature of A-150 plastic, is correlated with the relative humidity of the facility, and is greater than the humidity corrections for gas described in the literature. The data suggest that chamber calibration should be performed at least weekly to accommodate these variations.     

Preliminary evaluations of the undesirable patient dose from a BNCT treatment at the ENEA-TAPIRO reactor

Boron neutron capture therapy (BNCT) is an experimental technique for the treatment of certain kinds of tumors. Research in BNCT is performed utilizing both thermal and epithermal neutron beams. Epithermal neutrons (0.4 eV-10 keV) penetrate more deeply into tissue and are thus used in non-superficial clinical applications such as the brain glioma. In the last few years, the fast reactor TAPIRO (ENEA-Casaccia Rome) has been employed as a neutron source for research into BNCT applications. Recently, an 'epithermal therapeutic column' has been designed and its construction has been completed. The Monte Carlo code MCNPX was employed to optimize the design of the column and to evaluate the dose profiles and the therapeutic parameters in the cranium of the anthropomorphic phantom ADAM. In the same context, some preliminary evaluations of the undesirable doses to the patient were performed with MCNPX. A hermaphrodite phantom derived from ADAM and EVA was employed to evaluate the energy deposition in some organs during a standard BNCT treatment. The total dose consists of the contributions from the primary neutron beam, the neutron interactions with boron and the neutron induced photons generated in the epithermal column structures and in the patient's tissues. The paper summarizes the computational procedure and provides a general dosimetric framework of the patient radiological protection aspects related to a BNCT treatment scenario at the TAPIRO reactor.     

Characterisation of an accelerator-based neutron source for BNCT versus beam energy

Neutron capture in ¹⁰B produces energetic alpha particles that have a high linear energy transfer in tissue. This results in higher cell killing and a higher relative biological effectiveness compared to photons. Using suitably designed boron compounds which preferentially localize in cancerous cells instead of healthy tissues, boron neutron capture therapy (BNCT) has the potential of providing a higher tumor cure rate within minimal toxicity to normal tissues. This clinical approach requires a thermal neutron source, generally a nuclear reactor, with a fluence rate sufficient to deliver tumorcidal doses within a reasonable treatment time (minutes). Thermal neutrons do not penetrate deeply in tissue, therefore BNCT is limited to lesions which are either superficial or otherwise accessible. In this work, we investigate the feasibility of an accelerator-based thermal neutron source for the BNCT of skin melanomas. The source was designed via MCNP Monte Carlo simulations of the thermalization of a fast neutron beam, generated by 7 MeV deuterons impinging on a thick target of beryllium. The neutron field was characterized at several deuteron energies (3.0–6.5 MeV) in an experimental structure installed at the Van De Graaff accelerator of the Laboratori Nazionali di Legnaro, in Italy. Thermal and epithermal neutron fluences were measured with activation techniques and fast neutron spectra were determined with superheated drop detectors (SDD). These neutron spectrometry and dosimetry studies indicated that the fast neutron dose is unacceptably high in the current design. Modifications to the current design to overcome this problem are presented.     

A measuring system with a recombination chamber for neutron dosimetry around medical accelerators

A measuring system for dosimetry of neutrons generated around medical electron accelerators is proposed. The system consists of an in-phantom tissue-equivalent recombination chamber and associated electronics for automated control and data acquisition. A second ionization chamber serves as a monitor of photon radiation. Two quantities are determined by the recombination chamber--the total absorbed dose and the recombination index of radiation quality. The ambient dose equivalent, H*(10), or neutron absorbed dose in an appropriate phantom, can be then derived from the measured values. Tests of the system showed that a 0.5% dose contribution of neutrons to the absorbed dose of photons could be detected and estimated under laboratory conditions. Preliminary tests at the 15 MV Varian Clinac 2300C/D medical accelerator confirmed that the measuring system could be used under clinical conditions. The H*(10) of the mixed radiation was determined with an accuracy of approximately 10%.     

Calibration of the borated ion chamber at NIST reactor thermal column

In boron neutron capture therapy and boron neutron capture enhanced fast neutron therapy, the absorbed dose of tissue due to the boron neutron capture reaction is difficult to measure directly. This dose can be computed from the measured thermal neutron fluence rate and the (10)B concentration at the site of interest. A borated tissue-equivalent (TE) ion chamber can be used to directly measure the boron dose in a phantom under irradiation by a neutron beam. Fermilab has two Exradin 0.5 cm(3) Spokas thimble TE ion chambers, one loaded with boron, available for such measurements. At the Fermilab Neutron Therapy Facility, these ion chambers are generally used with air as the filling gas. Since alpha particles and lithium ions from the (10)B(n,alpha)(7)Li reactions have very short ranges in air, the Bragg-Gray principle may not be satisfied for the borated TE ion chamber. A calibration method is described in this paper for the determination of boron capture dose using paired ion chambers. The two TE ion chambers were calibrated in the thermal column of the National Institute of Standards and Technology (NIST) research reactor. The borated TE ion chamber is loaded with 1,000 ppm of natural boron (184 ppm of (10)B). The NIST thermal column has a cadmium ratio of greater than 400 as determined by gold activation. The thermal neutron fluence rate during the calibration was determined using a NIST fission chamber to an accuracy of 5.1%. The chambers were calibrated at two different thermal neutron fluence rates: 5.11 x 10(6) and 4.46 x 10(7)n cm(-2) s(-1). The non-borated ion chamber reading was used to subtract collected charge not due to boron neutron capture reactions. An optically thick lithium slab was used to attenuate the thermal neutrons from the neutron beam port so the responses of the chambers could be corrected for fast neutrons and gamma rays in the beam. The calibration factor of the borated ion chamber was determined to be 1.83 x 10(9) +/- 5.5% (+/- 1sigma) n cm(-2) per nC at standard temperature and pressure condition.     

Dose measuring system for boron neutron capture therapy

Dose measuring systems for boron neutron capture therapy (BNCT) of brain tumors are presented. The systems are a real-time monitoring system, an integral measuring system and a ¹⁰B concentration measuring system. The real-time monitoring with a small PN junction silicon detector made it possible to simultaneously measure the thermal neutron flux and the gamma dose rate in a patient during neutron therapy. Another monitoring of dose equivalents of thermal neutrons and gamma rays was performed with a BGO scintillation detector connected to an optical fiber. The accurate neutron fluence and gamma dose were determined with the integral measurements of the foil activation method and thermoluminescent dosimeters (TLDs) after irradiation. Kerma doses of thermal neutrons and gamma-rays were also measured with the TLD at the same time. Preliminary measurements of ¹⁰B concentration in tissue and blood of a patient were carried out by prompt gamma-ray spectroscopy.     

Gel dosimetry in the BNCT facility for extra-corporeal treatment of liver cancer at the HFR Petten

A thorough evaluation of the dose inside a specially designed and built facility for extra-corporeal treatment of liver cancer by boron neutron capture therapy (BNCT) at the High Flux Reactor (HFR) Petten (The Netherlands) is the necessary step before animal studies can start. The absorbed doses are measured by means of gel dosemeters, which help to validate the Monte Carlo simulations of the spheroidal liver holder that will contain the human liver for irradiation with an epithermal neutron beam. These dosemeters allow imaging of the dose due to gammas and to the charged particles produced by the (10)B reaction. The thermal neutron flux is extrapolated from the boron dose images and compared to that obtained by the calculations. As an additional reference, Au, Cu and Mn foil measurements are performed. All results appear consistent with the calculations and confirm that the BNCT liver facility is able to provide an almost homogeneous thermal neutron distribution in the liver, which is a requirement for a successful treatment of liver metastases.     

Brain tumour and infiltrations dosimetry of boron neutron capture therapy combined with 252Cf brachytherapy

This article presents a dosimetric investigation of boron neutron capture therapy (BNCT) combined with (252)Cf brachytherapy for brain tumour control. The study was conducted through computational simulation in MCNP5 code, using a precise and discrete voxel model of a human head, in which a hypothetical brain tumour was incorporated. A boron concentration ratio of 1:5 for healthy-tissue: tumour was considered. Absorbed and biologically weighted dose rates and neutron fluency in the voxel model were evaluated. The absorbed dose rate results were exported to SISCODES software, which generates the isodose surfaces on the brain. Analyses were performed to clarify the relevance of boron concentrations in occult infiltrations far from the target tumour, with boron concentration ratios of 1:1 up to 1:50 for healthy-tissue:infiltrations and healthy-tissue:tumour. The average biologically weighted dose rates at tumour area exceed up to 40 times the surrounding healthy tissue dose rates. In addition, the biologically weighted dose rates from boron have the main contribution at the infiltrations, especially far from primary tumour. In conclusion, BNCT combined with (252)Cf brachytherapy is an alternative technique for brain tumour treatment because it intensifies dose deposition at the tumour and at infiltrations, sparing healthy brain tissue.     

Filtered fast neutron irradiation system using Texas A&M University Nuclear Science Center Reactor

A heavily filtered fast neutron irradiation system (FNIS) was developed for a variety of applications, including the study of long-term health effects of fast neutrons by evaluating the biological mechanisms of damage in cultured cells and living animals such as rats or mice. This irradiation system includes an exposure cave made with a lead–bismuth alloy, a cave positioning system, a gamma and neutron monitoring system, a sample transfer system, and interchangeable filters. This system was installed in the irradiation cell of the Texas A&M University Nuclear Science Center Reactor (NSCR). For a realistic modeling of the NSCR, the irradiation cell, and the FNIS, this study used the Monte Carlo N-Particle (MCNP) code and a set of high-temperature ENDF/B-VI continuous neutron cross-section data. Sensitivity analysis was performed to find the characteristics of the FNIS as a function of the thickness of the lead–bismuth alloy. A paired ion chamber system was constructed with a tissue-equivalent plastic (A-150) and propane gas for total dose monitoring and with graphite and argon for gamma dose monitoring. This study, in addition, tested the Monte Carlo modeling of the FNIS system, as well as the performance of the system by comparing the calculated results with experimental measurements using activation foils and paired ion chambers.     

Use of the CT images for BNCT calculation: development of BNCT treatment planning system and its applications to dose calculation for voxel phantoms

A BNCT (Boron Neutron Capture Therapy) treatment planning system (BTPS) was developed for BNCT study and treatment planning. Three kinds of CT images, VHP, PINNACLE and DICOM images, were employed to make voxel phantoms for BNCT patient treatment using the BTPS. The thermal neutron, fast neutron, gamma and boron doses are calculated and background, tissue, and tumour doses for idealised standard reactor neutron field (ISRNF) neutron beam were calculated by using BTPS and MCNP code. It was noted that the total computing times needed for BNCT analysis could be greatly reduced since the BTPS system provides a dose analysis tool and a lengthy MCNP input in a short time. It is, thus, expected that the BTPS can significantly contribute the BNCT study for the treatment of patients.     

硼中子俘获治疗人脑胶质母细胞瘤的前景和困惑

硼中子俘获疗法是一种可以选择性杀伤肿瘤细胞的放射疗法,其产生的α粒子对临床治疗新诊断和复发的脑胶质母细胞瘤有较好的疗效.发达国家20世纪五六十年代就已进入临床试验,但一直受到硼携带载体和中子源发展的限制.现就其治疗脑胶质母细胞瘤的前景做一综述.     

Neutron production in tissue-like media and shielding materials irradiated with high-energy ion beams

Secondary neutrons produced in high-energy therapeutic ion beams require special attention since they contribute to the dose delivered to patient, both to tumour and to the healthy tissues. Moreover, monitoring of neutron production in the beam line elements and the patient is of importance for radiation protection aspects around ion therapy facility. Monte Carlo simulations of light ion transport in the tissue-like media (water, A-150, PMMA) and materials of interest for shielding devices (graphite, steel and Pb) were performed using the SHIELD-HIT and MCNPX codes. The capability of the codes to reproduce the experimental data on neutron spectra differential both in energy and angle is demonstrated for neutron yield from the thick targets. Both codes show satisfactory agreement with the experimental data. The absorbed dose due to neutrons produced in the water and A-150 phantoms is calculated for proton (200 MeV) and carbon (390 MeV/u) beams. Secondary neutron dose contribution is approximately 0.6% of the total dose delivered to the phantoms by proton beam and at the similar level for both materials. For carbon beam the neutron dose contribution is approximately 1.0 and 1.2% for the water and A-150 phantoms, respectively. The neutron ambient dose equivalent, H(10), was determined for neutrons leaving different shielding materials after irradiation with ions of various energies.     

Recombination chambers filled with different gases--studies of possible application for BNCT beam dosimetry

Recombination microdosimetric method (RMM), based on the phenomenon of initial recombination of ions is applied to determine the distribution of the absorbed dose versus linear energy transfer (LET). Usually, the recombination chambers used for RMM are filled with tissue-equivalent gas, but the response of the device can be adjusted to the actual needs by the use of different gases. Using a graphite chamber filled with nitrogen and 10BF3 it was shown that RMM can also be used with chambers containing these gases. This opens the possibility of designing a recombination chamber for the determination of the dose fractions due to gamma radiation, fast neutrons, neutron capture on nitrogen and high-LET particles from the (n,10B) reaction in simulated tissue with different contents of 10B. It was also necessary to improve the method for the determination of initial recombination at low polarising voltages, when volume-recombination and back-diffusion of ions are considerably high.     

Shielding evaluation of a medical linear accelerator vault in preparation for installing a high-dose rate 252Cf remote afterloader

In support of the effort to begin high-dose rate 252Cf brachytherapy treatments at Tufts-New England Medical Center, the shielding capabilities of a clinical accelerator vault against the neutron and photon emissions from a 1.124 mg 252Cf source were examined. Outside the clinical accelerator vault, the fast neutron dose equivalent rate was below the lower limit of detection of a CR-39 etched track detector and below 0.14 +/- 0.02 muSv h(-1) with a proportional counter, which is consistent, within the uncertainties, with natural background. The photon dose equivalent rate was also measured to be below background levels (0.1 muSv h(-1)) using an ionisation chamber and an optically stimulated luminescence dosemeter. A Monte Carlo simulation of neutron transport through the accelerator vault was performed to validate measured values and determine the thermal-energy to low-energy neutron component. Monte Carlo results showed that the dose equivalent rate from fast neutrons was reduced by a factor of 100,000 after attenuation through the vault wall, and the thermal-energy neutron dose equivalent rate would be an additional factor of 1000 below that of the fast neutrons. Based on these findings, the shielding installed in this facility is sufficient for the use of at least 5.0 mg of 252Cf.     

Alanine and TLD coupled detectors for fast neutron dose measurements in neutron capture therapy (NCT)

A method was investigated to measure gamma and fast neutron doses in phantoms exposed to an epithermal neutron beam designed for neutron capture therapy (NCT). The gamma dose component was measured by TLD-300 [CaF2:Tm] and the fast neutron dose, mainly due to elastic scattering with hydrogen nuclei, was measured by alanine dosemeters [CH3CH(NH2)COOH]. The gamma and fast neutron doses deposited in alanine dosemeters are very near to those released in tissue, because of the alanine tissue equivalence. Couples of TLD-300 and alanine dosemeters were irradiated in phantoms positioned in the epithermal column of the Tapiro reactor (ENEA-Casaccia RC). The dosemeter response depends on the linear energy transfer (LET) of radiation, hence the precision and reliability of the fast neutron dose values obtained with the proposed method have been investigated. Results showed that the combination of alanine and TLD detectors is a promising method to separate gamma dose and fast neutron dose in NCT.