Microdosimetry for the characterization of the THOR epithermal neutron beam

The epithermal neutron beam of the Tsing Hua Open-pool Reactor (THOR) was constructed for the study of boron neutron capture therapy (BNCT). The THOR epithermal neutron beam was mainly composed of thermal neutrons, fast neutrons, and photons. For fast neutrons and photons, the absorbed dose and the relative biological effectiveness (RBE) were used to characterize radiation dose and radiation quality. The short-ranged alpha particles and lithium ions produced from ¹⁰B(n,α)⁷Li reactions in the BNCT required cellular- and micro-dosimetry characterizations. Due to the non-uniform microdistribution of boron in cells, these characterizations should depend on the source–target geometry. In this case, the geometry-dependent specific cellular dose and lineal energy could be used to describe radiation dose and radiation quality. In the present work, cellular- and micro-dosimetry were studied for the THOR epithermal neutron beam. The specific cellular dose and lineal energy were calculated for thermal neutron-induced α-particles and ⁷Li-ions with different source–target geometry and various cell sizes. Applying the linear energy dependent-biological weighting function, the geometry-dependent RBE of thermal neutron-induced heavy particles was determined. Finally, the effective RBE of the THOR epithermal neutron beam was estimated for tumors and normal tissues of specified ¹⁰B concentrations. This effective RBE should be multiplied by the total absorbed dose to determine the corresponding biological dose required in the treatment planning.     

The angular and spatial distributions of the thermal neutron source description of the THOR BNCT beam

This paper presents a way to determine the angular and spatial distributions of the thermal neutron source strength of a boron neutron capture therapy (BNCT) beam. The experiments applied 1) the indirect neutron radiography, 2) the cadmium difference method, and 3) the instrumental neutron activation analysis. The measured data were processed by the spectrum deconvolution technique to resolve into a proper set of angular and spatial distributions. This paper took the epithermal neutron beam of the BNCT facility at the Tsing Hua Open-pool Reactor as an example.     

基于3.5 MeV射频四极质子加速器硼中子俘获治疗装置的束流整形体设计

在硼中子俘获治疗(BNCT)装置中,束流整形体(BSA)的作用是将中子源产生的快中子束流慢化至超热中子能区(0.5 eVE10 keV),并尽可能减弱快中子、热中子和γ射线的成分,同时保证中子的方向性,其设计与优化是BNCT装置设计工作的核心内容之一.本文采用3.5 MeV,10 mA的质子束轰击锂靶,由核反应~7Li(p,n)~7Be产生的中子为源项,针对BSA的慢化体材料和结构、γ屏蔽层和热中子吸收层的厚度等参数进行蒙特卡罗模拟设计与优化.研究发现,采用Fluental和LiF两种慢化材料间隔2 cm层状堆叠的三明治BSA构型,在保证快中子剂量成分(D_f/φ_(epi)),γ剂量成分(D_γ/φ_(epi))和热中子比例φ_(th)/φ_(epi)满足IAEA-TECDOC-1223报告推荐要求的同时,在BSA出口处超热中子注量率优于单独使用Fluental和单独使用LiF的BSA设计.BSA出口处修正的Synder人头几何模型中的剂量分布计算结果显示:上述三明治构型的深度剂量分布与单独使用Fluental材料构型的结果基本相当,优于单独使用LiF构型,表明Fluental和LiF层状堆叠的三明治BSA构型是一种可行的BSA结构.     

The dose comparison between the THOR and HFR epithermal neutron beams

This study is a part of the beam comparison campaign, inter-center dose comparison, between boron neutron capture therapy facilities at the Tsing Hua Open-pool Reactor and the High Flux Reactor. The clinical information exchange can improve the dosimetry uncertainty for medical physics in a mixed field. The method of paired Mg(Ar) and TE(TE) ionization chambers was used to determine the gamma-ray and neutron dose rates. Furthermore, activation foils, including gold, copper, and manganese, were employed to estimate the thermal and epithermal neutron fluxes. Measurements were performed free in air and also in a PMMA phantom. All the chambers were calibrated using a ⁶⁰Co primary standard source at the Institute of Nuclear Energy Research, Taiwan. Spectrum dependent neutron sensitivity of TE(TE) chamber is one of the important parameters to evaluate dose components. The requested neutron spectra were calculated by the Monte Carlo code MCNP. The measured thermal neutron fluxes, gamma-ray and neutron dose rates of the THOR beam in the phantom were 2.6, 2.2, and 2.1 times of the HFR beam at 2.5-cm depth, respectively. The higher thermal neutron flux and neutron and gamma-ray dose rates are due to the higher epithermal neutron beam intensity of the THOR.     

基于2.5 MeV质子加速器BNCT装置的中子慢化材料性能模拟研究

基于加速器中子源的硼中子俘获治疗(Boron Neutron Capture Therapy, BNCT)是新一代的放射治疗方法,束流整形体(Beam Shaping Assembly, BSA)作为硼中子俘获治疗装置的重要组成部分,其作用是将中子源中的快中子束流慢化至超热中子能区(0.5 eV~10 keV),并尽可能减少快中子、热中子以及$\gamma $射线的成分,使其满足BNCT用于治疗的中子束要求。本工作基于蒙特卡罗软件包Geant4(Geometry and Tracking),以2.5 MeV,10 mA质子流强的7Li(p, n)7Be中子源为对象,研究分析了AlF₃ 、Fluental、Al₂O₃、Al作为慢化体材料时,不同的厚度对束流出口处的超热中子注量率、超热中子注量与热中子注量比值、快中子成分、$ \gamma $成分所产生的影响。计算表明,当选用厚度为25 cm的AlF₃作为慢化体材料时,经过整形慢化后的超热中子束的束流参数,均满足国际原子能机构(International Atomic Energy Agency, IAEA)的中子束流参数推荐值。     

基于加速器的多终端硼中子俘获治疗装置的束流整形组件设计

硼中子俘获治疗(Boron Neutron Capture Therapy,BNCT)是一种新型的精准放射治疗方法,束流整形组件(Beam Shaping Assembly,BSA)作为硼中子俘获治疗装置的重要组成部分,对于产生适用于BNCT的中子束至关重要.通过BSA可以将快中子慢化到适当的能量范围,并且减少其他不需...     

The use of recombination chambers at radiation therapy facilities

The paper presents an overview of the applications of recombination chambers for dosimetric measurements at radiotherapy facilities. The chambers were used at electron, proton and heavy ion accelerators, in the beam and in the vicinity of the accelerators at very different dose rates. The examples of measurements discussed in the paper include: the determination of the absorbed dose and radiation quality parameters of a 170 MeV proton beam and BNCT (boron neutron capture therapy) beam, neutron dose measurements at a phantom surface outside the beam of a 15 MV electron medical accelerator, determination of ambient dose equivalent, H1 (10) outside the irradiated phantom in the proton therapy treatment room at JINR (Dubna, Russia), and at working places outside the shielding of the heavy ion therapy facility at GSI (Darmstadt, Germany).     

Designing of the 14 MeV neutron moderator for BNCT

In boron neutron capture therapy (BNCT), the ratio of the fast neutron flux to the neutron flux in the tumor (RFNT) must be less than 3%. If a D-T neutron generator is used in BNCT, the 14 MeV neutron moderator must be optimized to reduce the RFNT. Based on the neutron moderation theory and the simulation results, tungsten, lead and diamond were used to moderate the 14 MeV neutrons. Satisfying RFNT of less than 3%, the maximum neutron flux in the tumor was achieved with a three-layer moderator comprised of a 3 cm thick tungsten layer, a 14 cm thick lead layer and a 21 cm thick diamond layer.     

MCNP simulation of the dose distribution in liver cancer treatment for BNC therapy

The Boron Neutron Capture Therapy (BNCT) is based on selective uptake of boron in tumour tissue compared to the surrounding normal tissue. Infusion of compounds with boron is followed by irradiation with neutrons. Neutron capture on ¹⁰B, which gives rise to an alpha particle and recoiled ⁷Li ion, enables the therapeutic dose to be delivered to tumour tissue while healthy tissue can be spared. Here, therapeutic abilities of BNCT were studied for possible treatment of liver cancer using thermal and epithermal neutron beam. For neutron transport MCNP software was used and doses in organs of interest in ORNL phantom were evaluated. Phantom organs were filled with voxels in order to obtain depth-dose distributions in them. The result suggests that BNCT using an epithermal neutron beam could be applied for liver cancer treatment.     

Thermal neutron calibration method using an intense neutron beam from JRR-3M

We have developed a thermal neutron calibration method using a reactor produced neutron beam in JRR-3M of the Japan Atomic Energy Agency. Neutron-induced prompt gamma ray analysis has usually been performed in this beam line. Neutron energy distributions with negligible contributions from epithermal neutrons were measured by a time-of-flight method with a chopper made of ⁶LiF powder. The thermal neutron flux was determined by a gold foil activation method. We found that the thermal neutron beam in JRR-3M was well suited for calibration, neutron detector development or neutron dosimetry.     

BNCT中子源用RFQ加速器

 分析了加速器作为硼中子俘获治疗(BNCT)中子源的优势，提出以射频四极场（RFQ）加速器作为BNCT用中子源的首选机型。对该RFQ的参数进行了选择，利用质子轰击锂靶近阈反应产生的前冲中子束能散低、散角小的优势，设定RFQ最终能量为1.9 MeV。采用“匹配均温”设计方法进行了此强流质子RFQ的束流动力学设计，并对设计方案进行了传输模拟，在入口归一化均方根发射度为0.25 mm·mrad、流强为100 mA时，束流传输效率为99.3％。选择合适厚度的锂靶，经过整形即可得到满足BNCT治疗需要的中子束。     

Study of the improvement of TLD cards for personal neutron dosimetry

In this work, personal thermoluminescence dosimeter (TLD) cards type of GN-6770 (holder type 8806) from Harshaw were used for personal neutron dosimetry. The response of the dosimeters has been determined in terms of the personal absorbed dose and personal dose equivalent for different neutron energy components, based on the recommendations of ICRP-60 and ICRU-49. Neutron irradiation was performed using a 5 mCi Am–Be neutron source. The TLD reader, type Harshaw 6600, was installed and calibrated for accurate neutron doses equivalent to gamma-ray doses. It was found that fast neutron doses measured by TLD (badges or cards) are in agreement with those measured by neutron TE (tissue equivalent gas) ionization chambers and neutron monitors. Thermal neutron doses measured by TLD cards were overestimated when compared with those measured by neutron monitors. Additional Cd was used to reduce thermal neutron doses to be in agreement with actual thermal doses. Other configurations for TLD crystals are also suggested for accurate thermal neutron dose measurements.     

The relative biological effectiveness of a high energy neutron beam for micronuclei induction in T-lymphocytes of different individuals

In assessing the radiation risk of personnel exposed to cosmic radiation fields as it pertains to radiological damage during travel in civilian aircrafts, it is particularly important to know the relative biological effectiveness (RBE) for high energy neutrons. It has been the subject of numerous investigations in recent years using different neutron energies and cytogenetic examinations. Variations in the radiosensitivity of white blood cells for different individuals are likely to influence the estimate of the relative biological effectiveness for high energy neutrons. This as such observations have been noted in the response of different cancer cell lines with varying inherent sensitivities. In this work the radiosensitivities of T-lymphocytes of different individuals to the p(66)/Be neutron beam at iThemba LABS were measured using micronuclei formations and compared to that noted following exposure to ⁶⁰Co γ-rays. The principle objective of this investigation was to establish if a relationship between neutron RBE and variation in biological response to ⁶⁰Co γ-rays for lymphocytes from different individuals could be determined. Peripheral blood samples were collected from four healthy donors and isolated lymphocytes were exposed to different doses of ⁶⁰Co γ-rays (1–5 Gy) and p(66)/Be neutrons (0.5–2.5 Gy). One sample per donor was not exposed to radiation and served as a control. Lymphocytes were stimulated using PHA and cultured to induce micronuclei in cytokinesis-blocked cells. Micronuclei yields were numerated using fluorescent microscopy. Radiosensitivities and RBE values were calculated from the fitted parameters describing the micronuclei frequency dose response data. Dissimilar dose response curves for different donors were observed reflecting varying inherent sensitivities to both neutron and gamma radiation. A clear reduction in the dose limiting RBE_M is noted for donors with lymphocytes more sensitive to γ-rays (p = 0.032, R² = 0.94). Unlike observations made with different cancer cell lines exposed to the same clinical neutron beam, the variations in neutron RBE observed in T-lymphocytes of different individuals is related to the cellular radioresistance to photons.     

硼中子俘获治疗的蒙特卡罗方法模拟

用通用蒙特卡罗程序MCNP模拟了粒子在人脑中的输运过程. 吸收剂量率主要来自以下四个反应:¹⁰B(n,α)⁷Li,¹⁴N(n,p)¹⁴C,¹H(n,γ)²D,快中子弹性散射反应.对肿瘤区的贡献主要来自硼中子吸收反应.结果表明,超热中子比热中子适合于深肿瘤的治疗,而热中子对浅肿瘤的治疗有优越性,比如皮肤癌.同确定论方法的结果相比,蒙特卡罗方法不失为一种模拟中子俘获治疗的好工具.     

基于蒙特卡罗方法的α粒子细胞S值计算

在放射性免疫治疗以及硼中子俘获治疗（BNCT）等放射性治疗过程中,粒子通过与人体组织材料相互作用产生次级电子将能量传递给人体组织,放射性核素在细胞尺度分布的不均匀性将严重影响靶区剂量分布。为深入了解放射性核素在细胞中不同位置分布对靶区剂量影响,采用基于历史凝聚算法的Monte Carlo 工具包Geant4编写了细胞S值计算程序。计算了2种细胞尺寸,12种粒子能量,3种源分布方式的细胞S值,与医学内照射剂量（MIRD）委员会解析算法的计算结果进行对比,发现两者差异在1%以内。证明了Geant4在m尺度下细胞剂量计算的可行性,并对BNCT治疗过程中产生的粒子(1.47 MeV与1.78 MeV)的细胞S值进行计算。     

10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure.     

Development of high-radiation-sensitive polymer gel for magnetic resonance imaging in three-dimensional dosimetry

We developed a high radiation sensitive polymer gel by modifying the amounts of the gel components and the temperature for the gel preparation. We evaluated its relaxation time linearity against dose and compared the measured dose distribution with the calculated one. For the relaxation time-dose linearity, irradiations were carried out with a linear accelerator using 6 MV photons and doses ranging from 0-5.0 Gy. The relationship between dose and R(2) value (reciprocal of T(2) relaxation time) was measured and it had good linearity over a wide range (0.3-5 Gy). The measured dose distributions were in good agreement with calculated ones. Since the present gel has higher sensitivity and it is synthesized more easily at lower cost than conventional polymer gels, we expect to see improved three-dimensional (3D) dosimetry using it.     

Assessment of cancer risk from neutron exposure – The ANDANTE project

The ANDANTE project began in January 2012 as a spin-off of results of an earlier Euratom project, ALLEGRO, designed to address the problems of medium- and long-term risks following radiotherapy. ANDANTE will investigate the relative risk of induction of cancer from exposure to neutrons compared to photons. The project will focus on three specific cancers that may be detected as second malignant neoplasms following paediatric radiotherapy: salivary gland, thyroid gland, and breast tissue. Stem cells from each of the types of tissue will be exposed to well characterised beams of both neutrons and photons. Biological markers of possible tumorigenesis will be used to develop RBE models for neutrons. The experimental beams will be measured in terms of fluence and energy spectra in order to provide date for a track structure model, which will be developed to simulate the exact experimental conditions and to explore the relationships between exposure parameters and response. The RBE model will be utilized in the assessment of follow-up data from paediatric photon radiotherapy patients. The out-of-beam mixed photon-neutron fields generated during proton therapy will be measured in phantoms, and an analytic algorithm will be developed for reconstructing the fields distant from the treatment site using data available from clinical records. One of the aims of the project is a critical analysis of the potential power of a multi-centre cohort of paediatric patients to give confidence in the neutron risk estimates in radiotherapy patients.This paper focuses on the challenges in the ANDANTE project posed by the need to know detailed neutron, photon, and charged particle fluences and energy spectra in order to determine the neutron RBE as a function of dose and energy.     

Novel applications of particle accelerators to radiotherapy

Charged hadrons (protons and heavier ions) have very definite advantages over photons as far as radiotherapy applications are concerned. They allow for much better spatial dose localization due to their charge, relatively high mass and nature of the energy deposition process. In the frame of an attempt to promote the introduction of hadrontherapy in Argentina we have installed and started using an external beam facility at our tandem accelerator TANDAR. The advantages of heavy ions can only be fully exploited for tumors of well defined localization. In certain types of malignancies, however, the region infiltrated by tumor cells is diffuse, with no sharp boundaries and with microscopic ramifications. In such cases (particularly in certain brain cancers) a more sophisticated scheme has been suggested called boron neutron capture therapy (BNCT). In this work, the use of the Tandar accelerator to produce neutrons for feasibility studies for BNCT through low-energy proton beams on a thick LiF target is being briefly described. Studies on the ¹³C(d,n) reaction and a comparison with other neutron-producing reactions are also mentioned. Simulation work to optimize an accelerator-based neutron production target is discussed. A project is being prepared to develop a small proton accelerator in Argentina. Technical specifications of this machine will be briefly discussed.     

The measurement using passive dosemeters of the neutron component of aircraft crew dose

The cosmic radiation field at aviation altitudes can be measured with simple passive detectors. The non-neutron component may be measured by means of thermoluminescence dosimetry or other techniques, and the neutron component may be measured using poly allyl diglycol carbonate (PADC) dosemeters as described in this paper. Effective dose from neutron radiation becomes the larger component for altitudes above about 10 km, in general. The dominance is more pronounced for higher latitudes. The neutron energies range up to the maximum of the incident protons, that is many GeV. However the majority of the dose is contributed by neutrons of a few hundred MeV and less, with two maxima in the fluence spectrum, one between 1 and 10 MeV and the other between 50 and 150 MeV. We have used PADC dosemeters, electrochemically etched, to estimate the neutron component of effective dose. Up to 50 dosemeters are used in a single measurement to obtain an estimate of sufficient precision for total neutron effective doses of 50 microSv and less. The neutron fluence response characteristics of the dosemeter have been measured up to 70 MeV. These are extrapolated up to 180 MeV. This extrapolation is validated, partially, by a comparison of measured and predicted readings in the CERN reference field. From the dosemeter readings for exposure on board aircraft, neutron fluence may be estimated assuming an isotropic radiation field and the estimated neutron fluence spectrum. The neutron fluence may then be converted to effective dose using published values of conversion coefficients with the same assumptions of isotropy and known fluence spectrum. For the measurement results reported here, the calculated spectrum for the CERN concrete shielded field is used.