硼中子俘获治疗(BNCT)设备中子束流质量控制检测项分析

目的通过对医院中子照射器(IHNI)的超热中子束流辐射特性参数和剂量学特性参数的检测, 为建立硼中子俘获治疗(BNCT)设备中子束流的质量控制检测方法提供参考。方法通过对比各项检测结果的不确定度与欧洲联合研究中心(EC-JRC)推荐的偏差值, 分析评估相应检测方法的可行性。结果超热中子注量率的不确定度为2.7%;热中子与超热中子注量率比值的不确定度为3.1%;快中子空气比释动能率与超热中子注量率比值的不确定度为9.3%;γ空气比释动能率与超热中子注量率比值的不确定度为8.7%;中子注量率空间分布的不确定度为2.7%;模体内热中子注量率的不确定度为1.8%;模体内中子和γ射线剂量率的不确定度分别为17.1%和4.0%。结论模体内中子剂量率测量结果不确定度高, 需要进一步研究该项检测方法来提高检测结果的准确度;其余检测项测量结果不确定度低, 检测结果准确度预期能满足欧洲联合研究中心的推荐允许偏差值, 检测方法可行。     

Monte Carlo simulations of therapeutic proton beams for relative biological effectiveness of double-strand break

Abstract

Purpose: The relative biological effectiveness (RBE) values relative to ⁶⁰Co for the induction of double-strand breaks (DSB) were calculated for therapeutic proton beams. RBE-weighted absorbed doses were determined at different depths in a water phantom for proton beams.

Materials and methods: The depth-dose distributions and the fluence spectra for primary protons and secondary particles were calculated using the FLUKA (FLUktuierende KAskade) MC (Monte Carlo) transport code. These spectra were combined with the MCDS (Monte Carlo damage simulation) code to simulate the spectrum-averaged yields of clustered DNA lesions. RBE for the induction of DSB were then determined at different depths in a water phantom for the unmodulated and modulated proton beams.

Results: The maximum RBE for the induction of DSB at 1 Gy absorbed dose was found about 1.5 at 0.5 cm distal to the Bragg peak maximum for an unmodulated 160 MeV proton beam. The RBE-weighted absorbed dose extended the biologically effective range of the proton beam by 1.9 mm. The corresponding maximum RBE value was inversely proportional to the proton beam energy, reaching a value of about 1.9 for 70 MeV proton beam. For a modulated 160 MeV proton beam, the RBE weightings were more pronounced near the spread-out Bragg peak (SOBP) distal edge.

Conclusions: It was demonstrated that a fast MCDS code could be used to simulate the DNA damage yield for therapeutic proton beams. Simulated RBE for the induction of DSB were comparable to RBE measured in vitro and in vivo. Depth dependent RBE values in the SOBP region might have to be considered in certain treatment situations.     

Experimental verification of beam characteristics for cyclotron-based epithermal neutron source (C-BENS)

A cyclotron-based epithermal neutron source has been developed for boron neutron capture therapy. This system consists of a cyclotron accelerator producing 1.1-mA proton beams with an energy of 30 MeV, a beam transport system coupled with a beryllium neutron production target, and a beam-shaping assembly (BSA) with a neutron collimator. In our previous work, the BSA was optimized to obtain sufficient epithermal neutron fluxes of using a Monte Carlo simulation code. In order to validate the simulation results, irradiation tests using multi-foil activation at the surface of a gamma-ray shield located behind the collimator and water phantom experiments using a collimated epithermal neutron beam were performed. It was confirmed experimentally that the intensity of the epithermal neutrons was 1.2×10⁹ cm⁻² s⁻¹.     

Changes in RBE of 14-MeV (d+T) neutrons for V79 cells irradiated in air and in a phantom: Is RBE enhanced near the surface?

Purpose

The relative biological effectiveness (RBE) for inacivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d+T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET⁶⁰Co photons.

Methods

Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, D₁=0.5–4 Gy.⁶⁰Co photons were used as reference radiation.

Results

The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE=2.3 at 4 Gy to RBE=3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom

Conclusion

The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of α particles from C(n,α) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

Dosimetric comparison at FiR 1 using microdosimetry, ionisation chambers and computer simulation.

Tissue equivalent proportional counter microdosimetry has been applied in the dosimetry of epithermal neutron beams as they can provide an independent and accurate method to determine gamma ray and neutron absorbed doses. Dosimetric comparison has been performed using a tissue equivalent proportional counter, dual ionisation chambers and DORT computer code at FiR 1 boron neutron capture therapy facility in Espoo, Finland. The three methods were applied to determine neutron and gamma ray absorbed doses at 25, 40, 60 and 120 mm depths along the beam centerline in a water-filled PMMA phantom. The determined absorbed doses were found to agree within the limits of the estimated uncertainties.     

Spatial and spectral characteristics of a compact system neutron beam designed for BNCT facility

The development of suitable neutron sources and neutron beam is critical to the success of Boron Neutron Capture Therapy (BNCT). In this work a compact system designed for BNCT is presented. The system consists of ²⁵²Cf fission neutron source and a moderator/reflector/filter/shield assembly. The moderator/reflector/filter arrangement has been optimized to maximize the epithermal neutron component which is useful for BNCT treatment of deep seated tumors with the suitably low level of beam contamination. The MCMP5 code has been used to calculate the different components of neutrons, secondary gamma rays originating from ²⁵²Cf source and the primary gamma rays emitted directly by this source at the exit face of the compact system. The fluence rate distributions of such particles were also computed along the central axis of a human head phantom.     

Effective dose evaluation for BNCT brain tumor treatment based on voxel phantoms

For BNCT treatments, in addition to tumor target doses, non-negligible doses will result in all the remaining organs of the body. This work aims to evaluate the effective dose as well as the average absorbed doses of each of organs of patients with brain tumor treated in the BNCT epithermal neutron beam at THOR. The effective doses were evaluated according to the definitions of ICRP Publications 60 and 103 for the reference male and female computational phantoms developed in ICRP Publication 110 by using the MCNP5 Monte Carlo code with the THOR-Y09 beam source. The effective dose acquired in this work was compared with the results of our previous work calculated for an adult hermaphrodite mathematical phantom. It was found that the effective dose for the female voxel phantom is larger than that for the male voxel phantom by a factor of 1.2–1.5 and the effective dose for the voxel phantom is larger than that for the mathematical phantom by a factor of 1.3–1.6. For a typical brain tumor BNCT, the effective dose was calculated to be 1.51 Sv and the average absorbed dose for eye lenses was 1.07 Gy.     

The RBE of the leakage radiation from the Hiletron neutron therapy unit

The RBE of the leakage radiation from the Hiletron 14.7 MeV neutron therapy unit has been measured using three sensitive biological systems in mice, which differ markedly in their radiobiological characteristics. These systems comprise type A spermatogonia and bone marrow stem cells, which are affected insignificantly by dose rate, and pigment abnormalities in hair follicles which are affected markedly by dose rate. For mice irradiated at 10 cm depth in a water phantom, the leakage radiation up to 40 cm from the beam axis was virtually as effective as the primary beam for the latter two biological systems, and for spermatogonia in mice when irradiated in air. At this distance, the total dose rate was about 0.2 cGy (rad) per minute (3% of that in the primary beam), and the gamma-ray component was about 70%. This equal effectiveness of the total dose for all three systems was considered fortuitous, and it implied high RBE values for equal effect with the small neutron component at far distances. Considering published data on RBE versus neutron energy, the evidence suggested either a positive interaction of neutron and gamma-ray components in killing bone marrow stem cells when the neutron component was less than 40% of the total dose, or an increased efficiency of neutrons when delivered at very low dose rates. However the components were additive in killing spermatogonia.     

Optimization of the target of an accelerator-driven neutron source through Monte Carlo numerical simulation of neutron and gamma transport by the PRIZMA code

At Budker Institute of Nuclear Physics, epithermal neutron source for neutron-capture therapy was built and neutron generation was realized. Source is based on tandem accelerator and uses near-threshold neutron generation from the reaction ⁷Li(p,n)⁷Be. The paper describes target optimization through the numerical simulation of proton, neutron and gamma transport by Monte Carlo method (PRIZMA code). It is shown that the near-threshold mode attractive due low activation provides high efficiency of the dose and acceptable therapeutic ratio and advantage depth.     

Microdosimetric Specification of Radiation Quality in Neutron Radiation Therapy

Summary

The neutron beams used by various radiotherapy centres are of widely differing energies, and differences of up to 50 per cent in the relative biological effectiveness (RBE) between different beams have been found in radiobiological experiments. Moreover, at some facilities RBE variations have been observed with increasing depth in a phantom. In spite of this evidence, there is no quantitative and uniquely accepted specification of radiation quality used in practice. The urgency of an adequate solution of this problem is illustrated by the fact that in radiation therapy the usual accuracy requirement for the quantity of radiation, i.e. the absorbed dose to be delivered to the tumour, is 3.5 per cent (1SD). In this paper a pragmatic solution for the specification of radiation quality for fast neutron therapy is proposed. It is based on empirical RBE versus lineal energy response or weighting functions. These were established by using existing radiobiological data and microdosimetric spectra measured under identical irradiation conditions at several European neutron irradiation units.     

In-phantom characterisation studies at the Birmingham Accelerator-Generated epIthermal Neutron Source (BAGINS) BNCT facility.

A broad experimental campaign to validate the final epithermal neutron beam design for the BNCT facility constructed at the University of Birmingham concluded in November 2003. The final moderator and facility designs are overviewed briefly, followed by a summary of the dosimetric methods and presentation of a small subset of the results from this campaign. The dual ionisation chamber technique was used together with foil activation to quantify the fast neutron, photon, and thermal neutron beam dose components in a large rectangular phantom exposed to the beam with a 12 cm diameter beam delimiter in place. After application of a normalisation factor, dose measurements agree with in-phantom MCNP4C predictions within 10% for the photon dose, within 10% for thermal neutron dose, and within 25% for the proton recoil dose along the main beam axis.     

252Cf裂变中子源在组织等效模体中的中子和γ辐射剂量分布的计算

目的：计算^252Cf裂变中子源的的中子和γ辐射在组织等模体内的剂量分布,为使用^252Cf裂变中子源进行中子放疗提供有用的剂量学参数。方法：建立^252Cf源和组织等效模体的三维几何计算模型,利用蒙特卡罗方法进行中子和γ辐射联合输运计算。结果：计算了两种医用^252Cf裂变中子源在水、血液、肌肉、皮肤、骨骼和肺组织等效材料构成的模体中距源不同距离点处的中子和γ辐射吸收剂量。结论：蒙特卡罗计算结果与文献数据以及使用双电离室实验测量的结果符合得较好。对^252Cf裂变中子源在5种组织材料构成的模体中中子和γ辐射的剂量分布进行了比较,使用水作为组织等效材料对^252Cf裂变中子源在在以肌肉、血液和皮肤构成的局部组织内的剂量分布进行模拟计算,可取得较可靠的结果。     

A phantom experiment for the evaluation of whole body exposure during BNCT using cyclotron-based epithermal neutron source (C-BENS)

At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics.In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported.     

~(252)Cf裂变中子源在组织等效模体中的中子和γ辐射剂量分布的计算

目的　计算2 5 2 Cf裂变中子源的中子和γ辐射在组织等效模体内的剂量分布 ,为使用2 5 2 Cf裂变中子源进行中子放疗提供有用的剂量学参数。方法　建立2 5 2 Cf源和组织等效模体的三维几何计算模型 ,利用蒙特卡罗方法进行中子和γ辐射联合输运计算。结果　计算了两种医用2 5 2 Cf裂变中子源在水、血液、肌肉、皮肤、骨骼和肺组织等效材料构成的模体中距源不同距离点处的中子和γ辐射吸收剂量。结论　蒙特卡罗计算结果与文献数据以及使用双电离室实验测量的结果符合得较好。对2 5 2 Cf裂变中子源在 5种组织材料构成的模体中中子和γ辐射的剂量分布进行了比较 ,使用水作为组织等效材料对2 5 2 Cf裂变中子源在以肌肉、血液和皮肤构成的局部组织内的剂量分布进行模拟计算 ,可取得比较可靠的结果。     

Evaluation of thermal neutron irradiation field using a cyclotron-based neutron source for alpha autoradiography

It is important to measure the microdistribution of ¹⁰B in a cell to predict the cell-killing effect of new boron compounds in the field of boron neutron capture therapy. Alpha autoradiography has generally been used to detect the microdistribution of ¹⁰B in a cell. Although it has been performed using a reactor-based neutron source, the realization of an accelerator-based thermal neutron irradiation field is anticipated because of its easy installation at any location and stable operation. Therefore, we propose a method using a cyclotron-based epithermal neutron source in combination with a water phantom to produce a thermal neutron irradiation field for alpha autoradiography. This system can supply a uniform thermal neutron field with an intensity of 1.7×10⁹ (cm⁻² s⁻¹) and an area of 40 mm in diameter. In this paper, we give an overview of our proposed system and describe a demonstration test using a mouse liver sample injected with 500 mg/kg of boronophenyl-alanine.     

Dose calculation from a D–D-reaction-based BSA for boron neutron capture synovectomy

Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D–D–reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12–30 times higher than the published values.     

Microdosimetric specification of radiation quality in neutron radiation therapy

The neutron beams used by various radiotherapy centres are of widely differing energies, and differences of up to 50 per cent in the relative biological effectiveness (RBE) between different beams have been found in radiobiological experiments. Moreover, at some facilities RBE variations have been observed with increasing depth in a phantom. In spite of this evidence, there is no quantitative and uniquely accepted specification of radiation quality used in practice. The urgency of an adequate solution of this problem is illustrated by the fact that in radiation therapy the usual accuracy requirement for the quantity of radiation, i.e. the absorbed dose to be delivered to the tumour, is 3.5 per cent (1 SD). In this paper a pragmatic solution for the specification of radiation quality for fast neutron therapy is proposed. It is based on empirical RBE versus lineal energy response or weighting functions. These were established by using existing radiobiological data and microdosimetric spectra measured under identical irradiation conditions at several European neutron irradiation units.     

In-phantom dosimetry using CaF2: Tm (TLD-300) ribbons

Parameters of calibrating CaF₂ : Tm for in-phantom dosimetry of therapeutically used fast neutron and ⁶⁰Co γ-ray beams have been studied. For ⁶⁰Co γ-ray beams the over-response, outside the main beam and at depths in phantom for large fields of irradiations is significant, and is higher for its 240°C glow peak than for its 150°C peak. The difference in the photon energy dependences of the two peaks of CaF₂ : Tm (Z_eff = 16.3), which is responsible for the above effect, is discussed. For therapeutically used cyclotron-produced fast neutron beams, the γ-ray absorbed dose component from photons of energy less than 200 keV is negligible.     

Al2O3剂量计在准直60Co γ线中的吸收剂量响应

目的 用Monte Carlo法研究Al₂O₃剂量计在准直⁶⁰Co γ线照射下在水中的吸收剂量响应特性。方法 用EGSnrc/DOSRZnrc 程序计算水体模中Al₂O₃剂量计的吸收剂量及剂量计相应位置上水的吸收剂量,并计算吸收剂量换算因子。剂量计元件用一个直径0.4 cm高0.1 cm的圆柱形Al₂O₃薄片表示,计算深度0.5~8.0 cm,入射粒子是准直后的⁶⁰Co γ线。结果 在研究的深度范围内,吸收剂量换算因子变化不大,平均值为1.143±0.006,最大偏差不大于1.0%。结论 在研究范围内,⁶⁰Co γ线中Al₂O₃剂量计的吸收剂量响应与剂量计在水体模中的深度无关,剂量响应稳定。     

RBE of d(50)-Be neutrons for induction of chromosome aberrations in Allium cepa onion roots

RBE/absorbed dose relationship of d(50)-Be neutrons was determined for the induction of chromosome aberrations in Allium cepa onion roots. Neutrons are produced at the cyclotron "Cyclone" by bombarding a thick beryllium target with 50 MeV deuterons. Two biological criteria were selected: (1) mean number of aberrations (mainly breaks) per cell in anaphase and telophase, (2) fraction of intact cells in anaphase and telophase. For the two criteria, RBE increases continuously from about 7 to 12 as the neutron absorbed dose decreases from 0.4 to 0.1 Gy. RBE values for the first criterion are slightly higher than for the second one. This observation is interpreted in terms of the analysis of the distribution of the aberrations in the cells. In logarithmic coordinates, RBE/absorbed dose relationships for the two criteria are almost linear with a slope close to -1/2. RBE values observed for induction of chromosome aberrations in Allium cepa are higher than those generally observed for biological effects related to mammalian cell lethality.