Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy

Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth-dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep-seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non-boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%.     

In-phantom dosimetry and spectrometry of photoneutrons from an 18 MV linear accelerator

A combination of three superheated drop detectors with different neutron energy responses was developed to evaluate dose-equivalent and energy distributions of photoneutrons in a phantom irradiated by radiotherapy high-energy x-ray beams. One of the three detectors measures the total neutron dose equivalent and the other two measure the contributions from fast neutrons above 1 and 5.5 MeV, respectively. In order to test the new method, the neutron field produced by the 10 cm X 10 cm x-ray beam of an 18 MV radiotherapy accelerator was studied. Measurements were performed inside a tissue-equivalent liquid phantom, at depths of 1, 5, 10 and 15 cm and at lateral distances of 0, 10, and 20 cm from the central axis. These data were used to calculate the average integral dose to the radiotherapy patient from direct neutrons as well as from neutrons transmitted through the accelerator head. The characteristics of the dosimeters were confirmed by results in excellent agreement with those of prior studies. Track etch detectors were also used and provided an independent verification of the validity of this new technique. Within the primary beam, we measured a neutron entrance dose equivalent of 4.5 mSv per Gy of photons. It was observed that fast neutrons above 1 MeV deliver most of the total neutron dose along the beam axis. Their relative contribution increases with depth, from about 60% at the entrance to over 90% at a depth of 10 cm. Thus, the average energy increases with depth in the phantom as neutron spectra harden.     

Benchmarking the MCNP code for Monte Carlo modelling of an in vivo neutron activation analysis system

The Monte Carlo computer code MCNP (version 4A) has been used to develop a personal computer-based model of the Swansea in vivo neutron activation analysis (IVNAA) system. The model included specification of the neutron source (252Cf), collimators, reflectors and shielding. The MCNP model was 'benchmarked' against fast neutron and thermal neutron fluence data obtained experimentally from the IVNAA system. The Swansea system allows two irradiation geometries using 'short' and 'long' collimators, which provide alternative dose rates for IVNAA. The data presented here relate to the short collimator, although results of similar accuracy were obtained using the long collimator. The fast neutron fluence was measured in air at a series of depths inside the collimator. The measurements agreed with the MCNP simulation within the statistical uncertainty (5-10%) of the calculations. The thermal neutron fluence was measured and calculated inside the cuboidal water phantom. The depth of maximum thermal fluence was 3.2 cm (measured) and 3.0 cm (calculated). The width of the 50% thermal fluence level across the phantom at its mid-depth was found to be the same by both MCNP and experiment. This benchmarking exercise has given us a high degree of confidence in MCNP as a tool for the design of IVNAA systems.     

Phantoms with 10BF3 detectors for boron neutron capture therapy applications

Two acrylic cube phantoms have been constructed for BNCT applications that allow the depth distribution of neutrons to be measured with miniature 10BF3 detectors in 0.5-cm steps beginning at 1-cm depth. Sizes and weights of the cubes are 14 cm, 3.230 kg, and 11 cm, 1.567 kg. Tests were made with the epithermal neutron beam from the patient treatment port of the Brookhaven Medical Research Reactor. Thermal neutron depth profiles were measured with a bare 10BF3 detector at a reactor power of 50 W, and Cd-covered detector profiles were measured at a reactor power of 1 kW. The resulting plots of counting rate versus depth illustrate the dependence of neutron moderation on the size of the phantom. But more importantly the data can serve as benchmarks for testing the thermal and epithermal neutron profiles obtained with accelerator-based BNCT facilities. Such tests could be made with these phantoms at power levels about five orders of magnitude lower than that required for the treatment of patients with brain tumors.     

Change in oxygen enhancement ratio with depth in tissue-equivalent material for a collimated beam of fast neutrons

Survival of reproductive capacity of murine leukaemia P-388 cells was assayed in vivo after the cells had been irradiated in vitro under aerobic or hypoxic conditions with collimated beams of X rays or 16 MeV D-Be fast neutrons at various depths in tissue-equivalent phantom material. The response to X-irradiation was the same in the absence of the phantom and at 8-7 cm depth. The response to fast neutrons under aerobic conditions was unchanged from 0 to 23 cm depth within the phantom. However, under hypoxic conditions, the dose-response curve for fast neutrons became significantly steeper with increasing depth in the phantom. The OER decreased from 2-0 in the absence of the phantom to 1-5 at 15 cm deep.     

Microdosimetric specification of the radiation quality of a d(48.5)+Be fast neutron therapy beam produced by a superconducting cyclotron

The proportional counter microdosimetric technique has been employed to quantify variations in the quality of a d(48.5)+Be fast neutron beam passing through a homogeneous water phantom. Single event spectra have been measured as a function of spatial location in the water phantom and field size. The measured spectra have been separated into component spectra corresponding to the gamma, recoil proton and alpha plus heavy recoil ion contribution to the total absorbed dose. The total absorbed dose normalized to the "monitor units" used in daily clinical use has been calculated from the measured spectra and compared to the data measured with calibrated ion chambers. The present measurements agree with the ion chamber data to within 5%. The RBE of the neutron beam is assumed to be proportional to the microdosimetric parameter y* for the dose ranges pertinent to fractionated neutron therapy. The relative variations in y*, assumed to be representative of variations in the RBE are mapped as a function of field size and spatial location in the phantom. A variation in the RBE of about 4% for points within and 8% for points outside a 10 cm x 10 cm field is observed. The variations in the RBE within the beam are caused by an increase in the gamma component with depth. An increase in the RBE of about 4% is observed with increasing field size which is attributed to a change in the neutron spectrum. Compared to the uncertainties in the prescribed dose, associated with uncertainties in the clinically used RBE, variation in the RBE between various tissues, and other dosimetric uncertainties caused by factors such as patient inhomogeneities, patient setup errors, patient motion, etc., the measured spatial RBE variations are not considered significant enough to be incorporated into the treatment planning scheme.     

Chemical composition of the lunar surface from neutron leakage fluxes

The neutron leakage fluxes from the lunar surface are calculated by Monte Carlo transport code based on Geant4. The integral fluxes of fast neutrons, epi-thermal neutrons and thermal neutrons are analyzed. Numerical results for 20 kinds of lunar soils and     

Application of fission track detectors to californium-252 neutron dosimetry in tissue near the radiation source

Fission track detectors were applied to a unique problem in neutron dosimetry. Measurements of neutron doses were required at locations within a tumor of 1 cm diameter implanted on the back of a mouse and surrounded by a square array of four 252Cf medical sources. Measurements made in a tissue-equivalent mouse phantom showed that the neutron dose rate to the center of the tumor was 2.18 rads micrograms-1 h-1 +/- 8.4%. The spatial variation of neutron dose to the tumor ranged from 1.88 to 2.55 rads micrograms-1 h-1. These measurements agree with calculated values of neutron dose to those locations in the phantom. Fission track detectors have been found to be a reliable tool for neutron dosimetry for geometries in which one wishes to know neutron dose values which may vary considerably over distances of 1 cm or less.     

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 inactivation 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 LET 60Co 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, Dt = 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 alpha particles from C(n, alpha) 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.     

Characteristics of neutron beam generated by 500 MeV proton beam

A neutron irradiation facility was constructed at PARMS, University of Tsukuba to produce an ultrahigh energy neutron beam with a depth dose distribution superior to an x-ray beam generated by a modern linac. This neutron beam was produced from the reaction on a thick uranium target struck by a 500 MeV proton beam from the booster synchrotron of the High Energy Physics Laboratory. The percentage depth dose of this neutron beam was nearly equivalent to that of x-rays around 20 MV and the dose rate was 15 cGy per minute. The relative biological effectiveness (RBE) of this neutron beam has been estimated using the cell inactivation effect and the HMV-I cell line. The survival curve of cells after neutron irradiation has a shoulder with n and Dq of 8 and 2.3 Gy, respectively. The RBE value at the 10(-2) survival level for the present neutron beam as compared with 137Cs gamma rays was 1.24. The results suggest that the biological effects of ultrahigh energy neutrons are not large enough to be useful, although the depth dose distribution of neutrons can be superior to that of high energy linac x-rays.     

Feasibility study: in vivo neutron activation for regional measurement of calcium using californium 252

The feasibility of using a collimated 252Cf neutron source to measure regional changes in skeletal calcium was tested because in vivo regional activation of diseased bone should offer advantages over the more widely reported total-body calcium measuring techniques. Regional activation allows examination of discrete regions where the greatest changes in calcium content occur. Additionally, a simpler radiation facility is required for regional studies. Using a 5.5-mug 252Cf source, thermal neutron flux and absorbed dose were measured in a tissue-equivalent phantom. Detection efficiency of 49Ca gamma rays for conditions simulating regional activation were measured using a 29-cm-diameter X 10-cm-thickness sodium iodide detector. These in vitro measurements indicate that a collimated 252Cf source can be used for regional neutron activation of the lower spine and legs. Preliminary calculations indicate that a 1-3-mg source provides adequate count rates for statistical accuracy with a bone marrow dosage acceptable for human patients and normal subjects.     

Total body chlorine: calibration of the in vivo neutron activation measurement

Total body chlorine (TBCI), used to estimate the extracellular space, is measured by delayed-gamma neutron activation (DGNA) using the reaction 37Cl(n, gamma)38Cl, at Brookhaven National Laboratory. During the calibration process, we noticed that different values were obtained when different amounts of Cl were placed in the phantom. This non-linear relationship is due to the thermal neutron flux suppression by the thermal neutron capture reaction 35Cl(n, gamma)36Cl. Monte Carlo simulations confirm the results of phantom measurements showing an inverse relationship between the Cl content in the phantom and the gamma-ray yield per gram Cl. Thus, it is important to calibrate the DGNA system for TBCl using phantom standards containing an amount of Cl close to that expected in the individual undergoing measurement.     

Calibration of a prototype in vivo total body composition analyser using 14 MeV neutron activation and the associated particle technique

A prototype in vivo total body composition analyser has been constructed for determining the total body contents of nitrogen (TBN), carbon (TBC) and oxygen (TBO) in young experimental animals such as sheep or pigs by 14 MeV neutron activation using a commercially available associated particle sealed tube neutron generator (APSTNG). The instrument was calibrated by scanning phantoms of different sizes in the mass range 10-36 kg, filled with a mixture of elements as found in a normal human body. Good agreement was found between the measured and expected values of N, O and C when two phantoms of similar dimensions but of different composition were scanned. With four 15 cm x 15 cm cross section and 45 cm long NaI(T1) gamma detectors and a radiation dose of approximately 20 microSv due to neutrons, the expected precisions for a 28 kg animal, CV% (based on counting statistics) are N: 9.3, C: 2.3 and O: 1.4.     

The FE-lspd model for electron beam dosimetry

The FE-lspd model is a two-component electron beam model that distinguishes between electrons that can be described by small-angle transport theory and electrons that are too widely scattered for small-angle transport theory to be applicable. The two components are called the primary beam and the laterally scattered primary distribution (lspd). The primary beam component incorporates a simple version of the Fermi-Eyges model and dominates dose calculations at therapeutic depths. The lspd component corrects erros in the lateral spreading of the primary beam component, thereby improving the accuracy by which the FE-lspd model calculates dose distribution in blocked fields. Comparisons were made between dose profiles and central-axis depth dose distributions in small fields calculated by the FE-lspd, Fermi-Eyges and EGS4 Monte Carlo models for a 10 MeV beam in a homogeneous water phantom. The maximum difference between the dose calculated using the FE-lspd model and EGS4 Monte Carlo is about 6% at a field diameter of about 1 cm, and less than 2% for field sizes greater than 3 cm diameter. The maximum difference between the Fermi-Eyges and Monte Carlo calculations is about 18% at a field diameter of about 2.5 cm. A comparison was made with the central-axis depth dose distribution measured in water for a 3 cm diameter field in a 10 MeV clinical electron beam. The errors in the dose distribution were found to be less than 2% using the FE-lspd model but almost 18% using the Fermi-Eyges model. A comparison was also made with pencil beam profiles calculated using the second-order Fermi-Eyges transport model.     

An empirical formula for scattered neutron components in fast neutron radiography

Scattering neutrons are one of the key factors that may affect the images of fast neutron radiography. In this paper, a mathematical model for scattered neutrons is developed on a cylinder sample, and an empirical formula for scattered neutrons is obtaine     

Dose and LET distributions due to neutrons and photons emitted from stopped negative pions

Computer calculations are made of the dose and LET distributions due to neutrons and photons produced when negative pions are stopped in a phantom. When negative pions are stopped in a material they undergo nuclear capture, resulting in the disintegration of the nucleus and the emission of short range charged particles and longer range neutrons and photons. The uncharged radiation constitutes a potentially large source of dose outside the treatment volume. A simple phantom consisting of a 0-25 m cube of either tissue or bone-equivalent material is set up with a 0-05 m cube in the centre to represent the treatment volume. Neutrons and photons are started in this central volume and transported across the phantom using Monte Carlo transport codes. Several different initial energy spectra for the neutrons are used, taken from experimental and theoretical data. These different spectra are found to give significant differences in dose, though the distance to the 80% dose level is always about 0-015 m. Order of magnitude differences in some LET regions are also found. The dose deposited by neutrons in bone is about 24% less than in soft tissue, the photon dose being small compared with the neutron dose.     

Examining Duct Leakage on Prestressed Concrete Bridges via a Multiple Neutron Sources Method

Tendon corrosion and the leakage of water through the grouting voids are important contributors to the degradation of prestressed concrete (PC) bridges. Therefore, leakage inspections are beneficial in determining whether a tendon is corroding. This work addresses the inspection of duct leakages on PC bridges using a special multiple neutron source method. This approach is based on the principle of elastic collision between fast neutrons and hydrogen atoms during the emergence of thermalization. Multiple neutron sources should be combined with multiple detectors and an appropriately extended detection time. The probability of capturing thermal neutrons can thus be increased to inspect PC duct leakage. An equation was derived from a combination of theoretical studies and experimental outcomes as a reference for properly selecting the numbers of neutron sources and detectors as well as the detection time. The experimental results show that this approach increases the detection depth of leakage within concrete.     

Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation

A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.     

Calretinin immunoreactivity in the developing olfactory system of the rainbow trout

OBJECTIVE: The objective of this study was to calculate and compare the effective dose and to estimate risk from the use of intraoral position-indicating devices of differing geometries. STUDY DESIGN: Thermoluminescent dosimeters were placed at selected sites in the upper portion of a tissue-equivalent human phantom to record the equivalent dose to weighted tissues and organs. The phantom was exposed to simulated complete mouth surveys with either a long (29.8 cm) or short (19.6 cm) round open-end position-indicating device, a long (35.3 cm) or short (23.3 cm) rectangular open-end position-indicating device, or a pointed (29.6 cm) closed-end position-indicating device. RESULTS: The effective dose was calculated as the sum of the equivalent doses to each organ or tissue multiplied by that organ or tissue's weighting factor. The salivary glands were included as part of the remainder. The effective dose ranged from 362 micro Sv for the pointed position-indicating device, to 63 micro Sv for both the long and the short rectangular position-indicating devices. CONCLUSIONS: These effective doses were calculated to represent a probability for stochastic effects that range in magnitude from 26 x 10(-6) to 4.6 x 10(-6).