Development of a low-energy monoenergetic neutron source for applications in low-dose radiobiological and radiochemical research

The McMaster University 3 MV KN Van de Graff accelerator facility primarily dedicated to in vivo neutron activation measurements has been used to produce moderate dose rates of monoenergetic fast neutrons of energy ranging from 150 to 600 keV with a small energy spread of about 25 keV (1σ width of Gaussian) by bombarding thin lithium targets with 2.00–2.40 MeV protons. The calculated dose rate of the monoenergetic neutrons produced using thin lithium targets as functions of beam energy, target thickness, lab angle relative to beam direction, and the solid angle subtended by the sample with the target has also been reported.     

An optimized neutron-beam shaping assembly for accelerator-based BNCT.

Different materials and proton beam energies have been studied in order to search for an optimized neutron production target and beam shaping assembly for accelerator-based BNCT. The solution proposed in this work consists of successive stacks of Al, polytetrafluoroethylene, commercially known as Teflon, and LiF as moderator and neutron absorber, and Pb as reflector. This assembly is easy to build and its cost is relatively low. An exhaustive Monte Carlo simulation study has been performed evaluating the doses delivered to a Snyder model head phantom by a neutron production Li-metal target based on the (7)Li(p,n)(7)Be reaction for proton bombarding energies of 1.92, 2.0, 2.3 and 2.5 MeV. Three moderator thicknesses have been studied and the figures of merit show the advantage of irradiating with near-resonance-energy protons (2.3 MeV) because of the relatively high neutron yield at this energy, which at the same time keeps the fast neutron healthy tissue dose limited and leads to the lowest treatment times. A moderator of 34 cm length has shown the best performance among the studied cases.     

The neutron therapy facility (DT, 14 MeV) at the radiotherapy department of the university hospital Hamburg-Eppendorf

The neutron therapy facility at the Radiotherapy Department of the University Hospital Hamburg-Eppendorf is described. This unit has been developed for clinical purposes according to the initiative and conception of the radiotherapist by AEG/Fed. Rep. of Germany and RDI/USA since 1969. The installation was completed at the beginning of 1974. Special treatment head and bed systems allow isocentric treatment and arc or multiple port therapy. For routine work operation conditions of 8 to 12 mA total beam current and 500 kV accelerating voltage are used. The neutron output at 12 mA is about 3.5 x 10(12) n/s giving a phantom dose rate of more than 20 rad/min for a field size of 17.8 x 17.8 cm2 at 80 cm source-skin distance. Technical installations for improvement of dose rate and half-life of the target are planned. Results of physical measurements about neutron energy distributions, contributions from neutrons and gamma-rays to the total absorbed dose, build-up effect, axial and lateral dose distributions as well as isodose profiles for different field sizes in a homogeneous phantom are presented. Bewteen February 1976 and November 1977 up to 180 patients have been treated.     

A fast neutron source for cultured cell irradiation.

Because of recent interest in the use of neutrons for radiotherapy, there has been an increased interest in the radiology of neutrons. In this irradiated cell study, a 1.3 MeV accelerator produced beam currents over 100 muA on the water-cooled 3-mm thick beryllium disk target. The monolayer of irradiated cells was neutron-shielded by about 700 kg of paraffin. The neutron energy spectrum for the 9Be(d,n)10B reaction was obtained, with an average neutron energy calculated to be between 3.3 and 3.5 MeV, and an average linear energy transfer calculated at more than 30 keV/micron.     

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.     

The Clatterbridge high-energy neutron therapy facility: specification and performance

A new high-energy neutron therapy facility has been installed at the Douglas Cyclotron Centre, Clatterbridge Hospital, Merseyside, in order to extend the clinical trials of fast neutrons initiated by the Medical Research Council. The neutron beam is produced by bombarding a beryllium target with 62 MeV protons. The target is isocentrically mounted with the potential for 360 degrees rotation and has a fully variable collimator. This gives a range of rectilinear field sizes from 5 cm x 5 cm to 30 cm x 30 cm. Basic neutron beam data including output, field flatness, penumbra and depth-dose data have been measured. For a 10 cm x 10 cm field, the 50% depth dose occurs at 16.2 cm in water and the output is 1.63 cGy microA-1 min-1 at the depth of dose maximum. The effectiveness of the target shielding and the neutron-induced radioactivity in the treatment head have also been measured. It is concluded that the equipment meets both the design specifications and also fully satisfies criticisms of earlier neutron therapy equipment. A full radiation survey of the centre was also carried out and it was found that radiation levels are low and present no significant hazard to staff.     

Characterization of ultra high energy neutron beam generated by 500 MeV proton beam

An ultra high energy neutron facility was constructed at PARMS, University of Tsukuba, to produce a neutron beam superior to an X-ray beam generated by a modern linac in terms of dose distribution. This has been achieved using the reaction on a thick uranium target struck by 500 MeV proton beam from the booster-synchrotron of High Energy Physics Laboratory. The percentage depth dose of this neutron beam is nearly equivalent to that of X-rays at around 20 MV and the dose rate of 15 cGy per minute. Relative biological effectiveness of this neutron beam has been estimated on the cell killing effect by the use of HMV-I cell line. Resultant survival curve of cells after the neutron irradiation shows the shoulder with n and Dq of 8 and 2.3 Gy, respectively. RBE value at 10(-2) survival level for the present neutron, compared with 137Cs gamma-rays is 1.24. The result suggests that the biological effects of high energy neutrons are not practically large enough whenever the depth dose distribution of neutrons becomes superior to high energy linac X-rays.     

Characteristics of the new THOR epithermal neutron beam for BNCT.

A characterization of the new Tsing Hua open-pool reactor (THOR) epithermal neutron beam designed for boron neutron capture therapy (BNCT) has been performed. The facility is currently under construction and expected in completion in March 2004. The designed epithermal neutron flux for 1 MW power is 1.7x10(9)n cm(-2)s(-1) in air at the beam exit, accompanied by photon and fast neutron absorbed dose rates of 0.21 and 0.47 mGys(-1), respectively. With (10)B concentrations in normal tissue and tumor of 11.4 and 40 ppm, the calculated advantage depth dose rate to the modified Snyder head phantom is 0.53RBE-Gymin(-1) at the advantage depth of 85 mm, giving an advantage ratio of 4.8. The dose patterns determined by the NCTPlan treatment planning system using the new THOR beam for a patient treated in the Harvard-MIT clinical trial were compared with results of the MITR-II M67 beam. The present study confirms the suitability of the new THOR beam for possible BNCT clinical trials.     

Build-up and depth-dose characteristics of different fast neutron beams relevant for radiotherapy.

Build-up and central axis depth-dose curves have been obtained for d(50) + Be and d + T neutron beams. Measurements carried out with the collimator opening covered with a layer of lead showed that for all three neutron beams the entrance dose is approximately 60% of the dose at the maximum. Consequently the skin-sparing properties of these neutron beams will be approximately equal and comparable to those for electron beam therapy. Central axis depth-dose curves have been established for d(50) + Be neutrons at 129 cm SSD, for p(42) + Be neutrons at 125 cm SSD and d + T neurtons and 60Co gamma rays at 80 cm SSD. The 50% dose values in a water phantom are at depths of 12.7 cm, 12.0 cm, 9.7 cm and 12.7 cm respectively, for field sizes of approximately 15 cm x 20 cm. Insertion of a 6 cm thick nylon filter in the p(42)+Be beam increases this value from 12.0 cm to 13.5 cm. The gamma component for the d+T neutron beam is higher than for the cyclotron beams.     

BNCT dose distribution in liver with epithermal D-D and D-T fusion-based neutron beams.

Recently, a new application of boron neutron capture therapy (BNCT) treatment has been introduced. Results have indicated that liver tumors can be treated by BNCT after removal of the liver from the body. At Lawrence Berkeley National Laboratory, compact neutron generators based on (2)H(d,n)(3)He (D-D) or (3)H(t,n)(4)He (D-T) fusion reactions are being developed. Preliminary simulations of the applicability of 2.45 MeV D-D fusion and 14.1 MeV D-T fusion neutrons for in vivo liver tumor BNCT, without removing the liver from the body, have been carried out. MCNP simulations were performed in order to find a moderator configuration for creating a neutron beam of optimal neutron energy and to create a source model for dose calculations with the simulation environment for radiotherapy applications (SERA) treatment planning program. SERA dose calculations were performed in a patient model based on CT scans of the body. The BNCT dose distribution in liver and surrounding healthy organs was calculated with rectangular beam aperture sizes of 20 cm x 20 cm and 25 cm x 25 cm. Collimator thicknesses of 10 and 15 cm were used. The beam strength to obtain a practical treatment time was studied. In this paper, the beam shaping assemblies for D-D and D-T neutron generators and dose calculation results are presented.     

15MV医用直线加速器光中子蒙特卡罗模拟

目的 研究高能医用直线加速器运行过程中因光核反应所形成的光中子辐射场。方法 利用蒙特卡罗(MC)程序模拟Clinic 2300CD型医用电子加速器15 MV X射线模式下光中子污染,掌握机头内不同位置光中子能谱和不同照射野下等中心处中子周围剂量当量变化,分析光中子在等中心平面内剂量分布和水模体中剂量衰减。结果 准直器关闭时,加速器机头内靶、主准直器、均整器和多叶准直器下表面的光中子平均能量分别为1.08、1.20、0.35、0.30MeV;等中心处中子周围剂量当量随着照射野的增大先增大后减少,在30 cm × 30 cm照射野下达到最大;随着测点在水模体中的深度增加,中子通量先增加后减小,而中子剂量却在逐渐减小;不同照射野下,光中子剂量率在水模体深度20 cm处,基本都接近本底。结论 探究高能医用直线加速器机头光中子谱和剂量分布特点,以及光中子在水模体内剂量沉积规律,能为进一步研究高能医用直线加速器光中子污染对患者产生的附加剂量提供支持。     

The munich fission neutron therapy facility MEDAPP at the research reactor FRM II

Purpose

At the new research reactor FRM II of the Technical University of Munich (TUM), the facility for Medical Applications (MEDAPP) was installed where fast neutrons are available as a beam for medical use.

Material and Methods

Thermal neutrons induce fission in a pair of uranium converter plates and generate fast neutrons which are guided to the patient by a beam tube. The maximum opening of the multi leaf collimator (MLC) is 30 × 20 cm² W × H. The beam is characterized by neutron-photon mixed beam phantom dosimetry. Specific safety measures are outlined.

Results

The neutron and gamma dose rates are 0.52 Gy/min and 0.20 Gy/min, respectively, in 2 cm depth of a water phantom. The half maximum depth of the neutron dose rate in water is 5.4 cm (mean neutron energy 1.9 ± 0.1 MeV). Conformity with the European Medical Devices Directive (MDD) 93/42/EEG, was proven so that MEDAPP has a CE mark and since February 2007 also the license for clinical operation.

Conclusion

The clinical neutron irradiations of malignant tumors, which were performed at the former research reactor FRM until 2000, can be continued at FRM II under improved conditions. First patients were irradiated in June 2007.     

High-frame rate imaging of two-phase flow in a thin rectangular channel using fast neutrons

We have demonstrated the feasibility of performing high-frame-rate, fast neutron radiography of air–water two-phase flows in a thin channel with rectangular cross section. The experiments have been carried out at the accelerator facility of the Physikalisch-Technische Bundesanstalt. A polychromatic, high-intensity fast neutron beam with average energy of 6 MeV was produced by 11.5 MeV deuterons hitting a thick Be target. Image sequences down to 10 ms exposure times were obtained using a fast-neutron imaging detector developed in the context of fast-neutron resonance imaging. Different two-phase flow regimes such as bubbly slug and churn flows have been examined. Two phase flow parameters like the volumetric gas fraction, bubble size and mean bubble velocities have been measured. The first results are promising, improvements for future experiments are also discussed.     

Accuracy of megavolt radiation dosimetry using thermoluminescent lithium fluoride.

The relative light output per Gy in polystyrene for roentgen beams of 6 and 42 MV and electrons between 2.2 and 34.5 MeV relative to 60Co gamma radiation is reported for different kinds of LiF dosemeters. The distribution of the absorbed dose inside a 0.25 and 0.4 mm thick LiF-teflon disc surrounded by polystyrene and irradiated with 60Co, 42 MV roentgen radiation and 39 MeV electrons was measured using 0.01 and 0.02 mm thick Lif-teflon discs. The measurements show that the absorbed dose distribution in the dosemeter depends on the energy of the radiation. When flat dosemeters were used, differences between the signals measured at the two orientations possible during read-out could easily amount to several per cent, and for this reason 0.4 mm and 0.5 mm LiF-Teflon discs were not trusted when the highest accuracy was required. The cavity theory by Burlin does not account for the phenomena caused by differences in electron scattering properties of the dosemeter and the phantom material. Some suggestions are presented for a different cavity theory for flat dosemeters dealing also with these phenomena. It describes the results to about the same degree of approximation as the Burlin theory, and fails to explain the observed energy dependence for electrons.     

Influence of dose rate on fast neutron OER and biological effectiveness determined for growth inhibition in Vicia faba

The influence of dose rate on the effectiveness of a neutron irradiation was investigated using growth inhibition in Vicia faba bean roots as biological system. d(50) + Be neutron beams produced at the cyclotron CYCLONE of the University of Louvain-la-Neuve were used, at high and low dose rate, by modifying the deuteron beam current. When decreasing the dose rate from 0.14 Gy.min-1 to 0.2 Gy.h-1, the effectiveness of the neutrons decreased down to 0.84 +/- 0.05 (dose ratio, at high and low dose rate. Dhigh/Dlow, producing equal biological effect). Control irradiations, with 60Co gamma-rays, indicated a similar reduction in effectiveness (0.84 +/- 0.03) when decreasing dose rate from 0.6 Gy.min-1 to 0.7 Gy.h-1. In previous experiments, on the same Vicia faba system, higher RBE values were observed for 252Cf neutrons, at low dose rate (RBE = 8.3), compared to different neutron beams actually used in external beam therapy (RBE = 3.2 - 3.6 for d(50) + Be, p(75) + Be and 15 MeV (d, T) neutrons). According to present results, this higher RBE has to be related to the lower energy of the 252Cf neutron spectrum (2 MeV), since the influence of dose rate was shown to be small. As far as OER is concerned, for d(50) + Be neutrons, it decreases from 1.65 +/- 0.12 to 1.59 +/- 0.09 when decreasing dose rate from 0.14 Gy.min-1 to 0.2 Gy.h-1. Control irradiations with 60Co gamma-rays have shown an OER decrease from 2.69 +/- 0.08 to 2.55 +/- 0.11 when decreasing dose rate from 0.6 Gy.min-1 to 0.7 Gy.h-1. These rather small OER reductions are within the statistical fluctuations.     

Changes of the cytogenetic effectiveness of the therapeutic ray of fast neutrons in water phantoms

Changes of cytogenetic effectiveness of the therapeutic ray of fast neutrons were studied in water phantom in the Medical-Biological Complex of CyclotronU-120 at the Institute for Nuclear Research of the Academy of Sciences of the Ukrainian SSR. Investigations were done in a culture of lymphocytes of the peripheral human blood by means of metaphase method to find out chromosomal aberrations. The neutrons were generated by firing a thick beryllium target with a 13.6 MeV-deuteron ray in the nuclear reaction 9Be (d,n) 10B. The investigated dose range was 25-220 cGy. The results of the studies demonstrate that the cytogenetic effectiveness of radiation is reduced with increasing depth of the water phantom. The maximum reduction of the effect was seen in a depth up to 6 cm, which is attached to absorption of low-energetic neutron fraction. The obtained results confirm necessity of to filter the therapeutically applicable beam of neutron radiation.     

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.     

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.     

Electron depth absorbed doses for small phantom depths. Comparison between different accelerators.

Depth dose distributions at small phantom depths in polystyrene were measured with a liquid ionization chamber at six different accelerators. The absorbed dose at 0.5 mm depth relative to the absorbed dose maximum in the central beam varied between 0.77 and 0.92 for 10 MeV electrons. Generally the surface absorbed dose increased with increasing energy or decreasing field size. Results from measurements off axis indicate small differences from the data available for the central beam.     

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.