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.     

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.     

Fast-neutron dose evaluation in BNCT with Fricke gel layer detectors

Boron neutron capture therapy (BNCT) is a cancer radiotherapy that uses epithermal and thermal neutron beams. The determination of the absorbed dose in healthy tissue, separating the various dose contributions having different radiobiological effectiveness (RBE) is of great importance for therapy planning. However, a standard code of practice has not yet been established because suitable methods for dosimetry in BNCT are still in progress.A study about the characterization of the epithermal column of the LVR-15 research reactor in ?e? (CZ) has been performed, in particular concerning the fast-neutron dose. This dose is not negligible and its determination is important owing to its high RBE. Fast-neutron and photon dose distributions in a water phantom have been measured by means of Fricke gel layer dosimeters. Even if gel layer dosimetry is not yet standardized, it is presently the only method for obtaining images of each dose contribution in BNCT neutron fields.The results were compared with values measured with thermoluminescence detectors, twin ionization chambers data taken from literature and Monte Carlo simulations.     

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 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.     

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.     

Characterization of a BNCT beam using neutron activation and indirect neutron radiography

This study aims to measure the neutronic characteristics of the 14-cm diameter boron neutron capture therapy beam at the Tsing Hua Open-pool Reactor and to provide essential information for the neutron source adjustment and validation. The measurements were performed both in air and inside a cubic PMMA phantom at the beam, with and without an 18-cm long extended PE collimator. The neutron intensity was determined by neutron activation analysis; the indirect neutron radiography and the cadmium difference method were coupled to provide the two-dimensional neutron flux distributions.According to the measurements, the angular distribution is highly forward for epithermal neutrons but much more divergent for thermal ones. A PE extended collimator will modify the beam characteristics and could benefit the treatment for head and neck tumors, which often needs higher therapeutical boron dose at the shallow region.     

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.     

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.     

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).     

Analysis of the relationship between neutron dose and Cerenkov photons under neutron irradiation through Monte Carlo method

To theoretically explore the feasibility of neutron dose characterized by Cerenkov photons, the relationship between Cerenkov photons and neutron dose in a water phantom was quantified using the Monte Carlo toolkit Geant4. Results showed that the ratio of the neutron dose deposited by secondary electrons above Cerenkov threshold energy to the total neutron dose is approximately a constant for monoenergetic neutrons from 0.01 eV to 100 eV. With the initial neutron beam energy from 0.01 eV to 100 eV, the number of Cerenkov photons has a good correlation with the total neutron dose along the central axis of the water phantom. The changes of neutron energy spectrum and mechanism analysis also explored at different depths. And the ratio of total neutron dose to the intensity of Cerenkov photons is independent of neutron energy for neutrons from 0.01 eV to 100 eV. These findings indicate that Cerenkov radiation also has potential in the application of neutron dose measurement in some specific fields.     

Boron thin films and CR-39 detectors in BNCT: A method to measure the 10B(n,α)7Li reaction rate

The working principle of the Boron Neutron Capture Therapy (BNCT) is the selective delivery of a greater amount of boron to the tumor cells than to the healthy ones, followed by the neutron irradiation that will induce the emission of α-particles and recoil ⁷Li nuclei through the ¹⁰B(n,α)⁷Li reaction. The objective of this work is to present a setup composed of a boron thin film coupled with CR-39. Alpha and ⁷Li particle coming from the boron films are used to quantify neutron boron reaction and are detected by CR-39. The nuclei compounding of this detector, H, C and O, will undergo fast neutrons reactions, which will be detected in the CR-39 itself. In this way, the ¹⁰B(n,α)⁷Li reaction and the contribution of fast neutrons to the flux can be determined at the same time. These measurements are essential for treatment planning as well as for studies of the biodistribution of ¹⁰B-carrier drugs and tissue microdosimetry. The boron films were deposited on stainless steel substrates through the sputtering technique and irradiated with thermal neutrons at the reactor IEA-R1 located at IPEN, São Paulo/SP, Brazil. Here we show the first results on the characterization of these thin films and calibration of the proposed setup.     

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.     

241Am-Be中子参考辐射的蒙特卡罗模拟研究

研究用于校准场所中子剂量监测仪表的241Am-Be中子参考辐射场计量特性。采用蒙特卡罗方法模拟了空气自由中子参考辐射(FRNR),GB/T 14055规定的最小尺寸中子参考辐射(SRNR)和实际中子参考辐射(ARNR)中不同检验点处中子周围剂量当量率、散射中子占比和能谱分布特征。研究结果表明,空气对FRNR中的剂量率和能谱分布影响小,近似为理想中子参考辐射;采用5%含硼聚乙烯作屏蔽的最小尺寸SRNR可减少热中子,降低散射中子占比,影锥法不适用于小尺寸中子参考辐射中对散射中子的修正;ARNR中的散射中子更少、占比更低,影锥法所得散射中子占比与理论值基本一致。     

Dosimetry and spectrometry at accelerator based neutron source for boron neutron capture therapy

An innovative accelerator-based neutron source for boron neutron capture therapy has started operation at the Budker Institute of Nuclear Physics, Novosibirsk. This facility is based on a compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915 MeV protons bombarding a lithium target using ⁷Li(p,n)⁷Be threshold reaction.In the article, techniques to detect neutron and gamma-rays at the facility are described. Gamma radiation is measured with NaI and BGO gamma-spectrometers. The total yield of neutrons is determined by measuring the 477 keV γ-quanta from beryllium decay. For the rough analysis of the generated neutron spectrum we used bubble detectors. As the epithermal neutrons are of interest for neutron capture therapy the NaI detector is used as activation detector. We plan to use a time-of-flight technique for neutron spectra measurement. To realize this technique a new solution of short time neutron generation is proposed.     

In-phantom neutron dose distribution for bladder cancer cases treated with high-energy photons

This work presents an estimation of the neutron dose distribution for common bladder cancer cases treated with high-energy photons of 15 MV therapy accelerators. Neutron doses were measured in an Alderson phantom, using TLD 700 and 600 thermoluminescence dosimeters, resembling bladder cancer cases treated with high-energy photons from 15 MV LINAC and having a treatment plan using the four-field pelvic box technique. Thermal neutron dose distribution in the target area and the surrounding tissue was estimated. The sensitivity of all detectors for both gamma and neutrons was estimated and used for correction of the TL reading. TLD detectors were irradiated with a Co⁶⁰ gamma standard source and thermal neutrons at the irradiation facility of the National Institute for Standards (NIS). The TL to dose conversion factor was estimated in terms of both Co⁶⁰ neutron equivalent dose and thermal neutron dose. The dose distribution of photo-neutrons throughout each target was estimated and presented in three-dimensional charts and isodose curves. The distribution was found to be non-isotropic through the target. It varied from a minimum of 0.23 mSv/h to a maximum of 2.07 mSv/h at 6 cm off-axis. The mean neutron dose equivalent was found to be 0.63 mSv/h, which agrees with other published literature. The estimated average neutron equivalent to the bladder per administered therapeutic dose was found to be 0.39 mSv Gy^?1, which is also in good agreement with published literature. As a consequence of a complete therapeutic treatment of 50 Gy high-energy photons at 15 MV, the total thermal neutron equivalent dose to the abdomen was found to be about 0.012 Sv.     

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.     

The influence of field size and off-axis distance on photoneutron spectra of the 18 MV Siemens Oncor linear accelerator beam

At present, high energy electron linear accelerators (LINACs) producing photons with energies higher than 10 MeV have a wide use in radiotherapy (RT). However, in these beams fast neutrons could be generated, which results in undesired contamination of the therapeutic beams. These neutrons affect the shielding requirements in RT rooms and also increase the out-of-field radiation dose to patients. The neutron flux becomes even more important when high numbers of monitor units are used, as in the intensity modulated radiotherapy. Herein, to evaluate the exposure of patients and medical personnel, it is important to determine the full radiation field correctly. A model of the dual photon beam medical LINAC, Siemens ONCOR, used at the University Hospital Centre of Osijek was built using the MCNP611 code. We tuned the model according to measured photon percentage depth dose curves and profiles. Only 18 MV photon beams were modeled. The dependence of neutron dose equivalent and energy spectrum on field size and off-axis distance in the patient plane was analyzed. The neutron source strength (Q) defined as a number of neutrons coming from the head of the treatment unit per x-ray dose (Gy) delivered at the isocenter was calculated and found to be 1.12 × 10¹² neutrons per photon Gy at isocenter. The simulation showed that the neutron flux increases with increasing field size but field size has almost no effect on the shape of neutron dose profiles. The calculated neutron dose equivalent of different field sizes was between 1 and 3 mSv per photon Gy at isocenter. The mean energy changed from 0.21 MeV to 0.63 MeV with collimator opening from 0 × 0 cm² to 40 × 40 cm². At the 50 cm off-axis the change was less pronounced. According to the results, it is reasonable to conclude that the neutron dose equivalent to the patient is proportional to the photon beam-on time as suggested before. Since the beam-on time is much higher when advanced radiotherapy techniques are used to fulfill high conformity demands, this makes the neutron flux determination even more important. We also showed that the neutron energy in the patient plane significantly changes with field size. This can introduce significant uncertainty in dosimetry of neutrons due to strong dependence of the neutron detector response on the neutron energy in the interval 0.1–5 MeV.     

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy.The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., ¹²C ions). It is reasonable to assume that the same types of patients would benefit from ¹²C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i.e., moving from neutrons to ¹²C ions and from photons to protons, respectively). An important area of research involves developing criteria to identify specific patients suitable for high-LET radiation. One promising technique is to measure the RBE of the cancer cell population in vitro mainly in head and neck tumors. Modern molecular imaging allows the identification of hypoxic or proliferative regions in the tumor. Special MRI examinations are also able to identify hypoxic regions. A promising predictive test recently initiated, is the study of non-repairable double strand breaks but the utility of the technique needs to be confirmed. The extensive experience with fast neutron therapy can greatly assist the transition to high-LET charged-particle therapy.