Neutron induced brachytherapy: a combination of neutron capture therapy and brachytherapy.

Brachytherapy is a widely used radiation therapy modality while neutron capture therapy is being intensely studied. These methods provide some advantages, but also have limitations that might be ameliorated by combining them. A technique that uses stable solid seeds or needles of Gd which are irradiated in vivo with neutrons has been evaluated. Monte Carlo calculations show that 5000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm3 with a three-plane implant of 9-Gd needles. The tumor to normal tissue advantage of this method is as good as brachytherapy using 60Co seeds. Measurements of prompt gamma dose with films and TLD-700s in a lucite phantom verify the Monte Carlo evaluation. Dose measurements of a Gd needle in air also show that Gd is promising for this form of brachytherapy.     

Transport calculations of depth-dose distributions for gadolinium neutron capture therapy.

Depth-dose distributions were calculated for thermal and epithermal neutron fluence and capture gamma ray dose rates using a two-dimensional neutron-coupled gamma-ray transport code (DOT 3.5) for gadolinium neutron capture therapy. The results show that (i) a capture gamma-ray dose rate of 10 Gy h-1 was obtained with a thermal neutron fluence rate of 1.5 x 10(9) cm-2 s-1 in a simulated tumour containing 5000 PPM gadolinium placed near the surface of a water phantom, (ii) deep-seated tumours may be treated with epithermal neutrons, and (iii) gadolinium neutron capture therapy appears to achieve comparable dose distributions to those of boron neutron capture therapy.     

Accelerator-based neutron brachytherapy

The development and evaluation of a new approach to neutron brachytherapy is described. This approach, accelerator-based fast neutron brachytherapy, involves the interstitial or intracavity insertion of a narrow, evacuated accelerator beam tube such that its tip, containing the neutron-producing target, is placed in or near the tumor. Tumor irradiation via brachytherapy should result in a reduction in the healthy tissue complication rate observed when poorly collimated and/or low energy external neutron beam are used for treatment. Use of a variable energy accelerator provides an advantage over isotope sources for neutron brachytherapy in that the neutron beam can be turned on and off and the neutron energy spectrum varied for different treatment applications. A prototype accelerator-based fast neutron brachytherapy device, 10 cm long and 6 mm outer diameter, has been constructed and evaluated in terms of its dosimetric output, treatment time, and practical feasibility. The prototype device is a tube-in-tube design with cooling water running between the inner and outer tubes to cool a beryllium target located at the tip of the inner tube. Cooling experiments were performed and coupled with Monte Carlo simulations to determine treatment times as a function of heat load for various neutron-producing reactions. Using the 9Be(d,n) 10B reaction at Ed= 1.5 MeV, 66 RBE-Gy (12 Gy physical dose) can be delivered to the boundary of a 4.5-cm-diam treatment volume in 8 min at a heat load of 130 W. Other reactions offer similar treatment times at somewhat higher bombarding energies and also show higher potential for dose enhancement with the boron-10 neutron capture reaction due to their softer neutron spectra. Dose distributions in a water phantom were measured with the prototype brachytherapy tube using the dual-ion chamber technique for the 9Be(d,n) 10B reaction at Ed = 1.5 MeV. The measurements and simulations agree within uncertainties and demonstrate that fast neutrons contribute more than 90% of the dose to the target volume.     

Dosimetry study of Re-188 liquid balloon for intravascular brachytherapy using polymer gel dosimeters and laser-beam optical CT scanner

Angioplasty balloons inflated with a solution of the beta-emitter Re-188 have been used for intravascular brachytherapy to prevent restenosis. Coronary stents are in extensive clinical use for the treatment of de novo atherosclerotic stenoses. In this study, the effect of an interposed stent on the dose distribution has been measured for Re-188 balloon sources using the proprietary BANG polymer gel dosimeters and He-Ne laser-beam optical CT scanner. In polymer gels, after ionizing radiation is absorbed, free-radical chain-polymerization of soluble acrylic monomers occurs to form an insoluble polymer. The BANG polymer gel dosimeters used in these measurements allow high resolution, precise, and accurate three-dimensional determination of dosimetry from a given source. Re-188 liquid balloons, with or without an interposed metallic stent, were positioned inside thin walled tubes placed in such a polymer dosimeter to deliver a prescribed dose (e.g., 15 Gy at 0.5 mm). After removing the balloon source, each irradiated sample was mounted in the optical scanner for scanning, utilizing a single compressed He-Ne laser beam and a single photodiode. In the absence of a stent, doses at points along the balloon axis, at radial distance 0.5 mm from the balloon surface and at least 2.5 mm from the balloon ends, are within 90% of the maximum dose. This uniformity of axial dose is independent of the balloon diameter and length. Dose rate and dose uniformity for intravascular brachytherapy with Re-188 balloon are altered by the presence of stent. The dose reduction by the stent is rather constant (13%-15%) at different radial distances. However, dose inhomogeneity caused by the stent decreases rapidly with radial distance.     

Use of low-pressure tissue equivalent proportional counters for the dosimetry of neutron beams used in BNCT and BNCEFNT

The absorbed dose in a phantom or patient in boron neutron capture therapy (BNCT) and boron neutron capture enhanced fast neutron therapy (BNCEFNT) is deposited by gamma rays, neutrons of a range of energies and the 10B reaction products. These dose components are commonly measured with paired (TE/Mg) ion chambers and foil activation technique. In the present work, we have investigated the use of paired tissue equivalent (TE) and TE+ l0B proportional counters as an alternate and complementary dosimetry technique for use in these neutron beams. We first describe various aspects of counter operation, uncertainties in dose measurement, and interpretation of the data. We then present measurements made in the following radiation fields: An epithermal beam at the University of Birmingham in the United Kingdom, a d(48.5) + Be fast neutron therapy beam at Harper Hospital in Detroit, and a 252Cf radiation field. In the epithermal beam, our measured gamma and neutron dose rates compare very well with the values calculated using Monte Carlo methods. The measured 10B dose rates show a systematic difference of approximately 35% when compared to the calculations. The measured neutron+gamma dose rates in the fast neutron beam are in good agreement with those measured using a calibrated A-150 TEP (tissue equivalent plastic) ion chamber. The measured 10B dose rates compare very well with those measured using other methods. In the 252Cf radiation field, the measured dose rates for all three components agree well with other Monte Carlo calculations and measurements. Based on these results, we conclude that the paired low-pressure proportional counters can be used to establish an independent technique of dose measurement in these radiation fields.     

Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.     

Performance characteristics of the MIT fission converter based epithermal neutron beam

A pre-clinical characterization of the first fission converter based epithermal neutron beam (FCB) designed for boron neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered beam were confirmed from neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal neutron flux is accompanied by very low specific photon and fast neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.     

A computational study into the use of polyacrylamide gel and A-150 plastic as brain tissue substitutes for boron neutron capture therapy

A precise evaluation of the dosimetric performance of epithermal neutron beams designed for boron neutron capture theory of brain tumours requires the use of a phantom material that closely matches brain tissue. The aim of this study was to investigate how well polyacrylamide gel (or PAG) and A- 150 plastic performed as substitutes for brain tissue compared with standard phantom materials such as water and polymethyl-methacrylate (or PMMA). Thermal neutron fluence, photon dose and epithermal neutron dose distributions were calculated for the epithermal neutron beam available at the University of Birmingham. The results presented in this paper show that the PAG provides a good simulation of radiation transport in the brain with differences from the real brain of +9.4%, - 10.8% and +5.1% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively. The polyacrylamide gel presented is therefore a promising substitute for brain tissue that can, as a dosimeter, provide a three-dimensional map of the absorbed dose delivered by the epithermal neutron beam. However, this study does not investigate the agreement between doses derived from magnetic resonance and physical doses for such gels. A- 150 plastic was shown to be a better substitute for brain tissue than PMMA, with differences from brain of -1.9%, -12.4% and - 13.2% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively, against +21.1%, -16.2% and +19.2% for PMMA. A-150 plastic should therefore be the material of choice for solid phantoms.     

Samarium-145: a new brachytherapy source

A new radiation source has been produced for brachytherapy, with radiation energies slightly above those of 125I, and a T1/2 of 340 d. This source, 145Sm, is produced by neutron irradiation of 144Sm (96.5% enriched). Decay is by electron capture with 140 K x-rays per 100 disintegrations in the energy region between 38-45 keV, plus 13 gamma-rays at 61 keV. These sources are encapsulated in Ti tubes, approximately 0.8 mm X 4.5 mm, and have been developed for temporary implantation in brain and ocular tumours. The 38-61 keV photons should make such sources easy to shield, while providing a dose distribution from source arrays somewhat more homogeneous than that from 125I. In addition, the 340 d half life of 145Sm permits its use for times significantly longer than that of 60 d 125I. While the 145Sm sources have been designed primarily for implantation in a brain tumour, they should be useful for almost any conventional brachytherapy application.     

A flattening filter for brachytherapy skin irradiation

Radioactive sources in close contact offer an alternative to superficial radiation in the treatment of skin lesions. A flattening filter was designed for a lead surface applicator to improve the skin dose distribution of a high dose rate (HDR) brachytherapy unit (Nucletron). At three heights from the opening (10, 15 and 25 mm) of the cylindrical applicator, the 192Ir source can be driven into the centre of the applicator. Thin sheets of lead foil (0.2 mm) were cut into circular shapes and placed in the opening to build a cylindrical cone that acts as a flattening filter. The shape of the cone was optimized in an iterative process using a spreadsheet and the resulting dose distribution under the applicator was determined using radiosensitive film. The use of the filter improved the dose distribution in a plane perpendicular to the beam axis to be within +/- 5% of the central axis dose. The present applicator and flattening filter together with an HDR brachytherapy unit offer an alternative for skin irradiation where a superficial unit is not available or will be replaced with a more flexible device. As the depth dose characteristics can be modified using different source-to-surface distances, the dose throughout the patient's skin can be shaped as desired by the radiation oncologist using a compensator design type approach.     

X-ray scalpel - a new device for targeted x-ray brachytherapy and stereotactic radiosurgery

The basic design and performance of a novel x-ray scalpel device for interstitial radiosurgery are reported. The x-ray scalpel is comprised of a capillary optics collimator conjugated with a high brilliance microfocus x-ray tube and a thin hollow needle (tip) attached to the collimator. The device is capable of producing a high dose rate (about 140 Gy min(-1) in water-like absorber at the exit window), 0.7 mm diameter, quasi-parallel beam that can be delivered to a targeted site by a minimally invasive procedure. Contrary to insertable x-ray tubes or radionuclides used in brachytherapy and complying with the 1/r(2) radiation attenuation law, the dose rate for a quasi-parallel beam decreases with distance as mu exp(-mu r), where mu is the energy-dependent linear attenuation coefficient in the exposed medium. Moreover, the shape, energy and the dose attenuation curve of the x-ray beam can be adjusted. Two versions of the x-ray scalpel device (5.4 keV and 20.2 keV) are described. We present results from our first test of the x-ray scalpel as a controllable source of focal radiation for producing radiation necrosis in rat brain tissue. Irradiation was transdurally delivered to the rat cerebral cortex for 10 min at a dose rate of 20 Gy min(-1).     

Study of the relative dose-response of BANG-3 polymer gel dosimeters in epithermal neutron irradiation

Polymer gels have been reported as a new, potential tool for dosimetry in mixed neutron-gamma radiation fields. In this work, BANG-3 (MGS Research Inc.) gel vials from three production batches were irradiated with 6 MV photons of a Varian Clinac 2100 C linear accelerator and with the epithermal neutron beam of the Finnish boron neutron capture therapy (BNCT) facility at the FiR 1 nuclear reactor. The gel is tissue equivalent in main elemental composition and density and its T2 relaxation time is dependent on the absorbed dose. The T2 relaxation time map of the irradiated gel vials was measured with a 1.5 T magnetic resonance (MR) scanner using spin echo sequence. The absorbed doses of neutron irradiation were calculated using DORT computer code, and the accuracy of the calculational model was verified by measuring gamma ray dose rate with thermoluminescent dosimeters and 55Mn(n,gamma) activation reaction rate with activation detectors. The response of the BANG-3 gel dosimeter for total absorbed dose in the neutron irradiation was linear, and the magnitude of the response relative to the response in the photon irradiation was observed to vary between different gel batches. The results support the potential of polymer gels in BNCT dosimetry, especially for the verification of two- or three-dimensional dose distributions.     

Transport calculations of the influence of physical factors on depth-dose distributions in boron neutron capture therapy

Distributions of thermal neutron fluence and capture gamma ray absorbed dose rates were evaluated, taking into consideration various physical factors relevant to boron neutron capture therapy. The use of a larger neutron irradiation aperture was associated with an increase in thermal neutron fluence and capture gamma ray absorbed dose rates. Radiation leakage was more significant with smaller phantoms. Attenuation of thermal neutron fluence rates by 10B suggested that there was an optimal 10B concentration (less than 100 PPM) for a given tumour. Deuteration of water allowed better penetration of thermal neutrons with less capture gamma rays and is potentially applicable for the treatment of deep-seated brain tumours.     

Beta dosimetry with microMOSFETs for endovascular brachytherapy

The aim of this study was to investigate if microMOSFETs are suitable for the dosimetry and quality assurance of beta sources. The microMOSFET dosimeters have been tested for their angular dependence in a 6 MeV electron beam. The dose rate dependence was measured with an iridium-192 afterloading source. By varying the source-to-surface distance (SSD) in a 12 MeV electron beam the dose rate dependence in an electron beam was also investigated. To measure a depth dose curve the dose rate at 2, 5, 8 and 12 mm distance from the beta source train axis was determined with the OPTIDOS and the microMOSFET detector. A comparison between the two detector types shows that the microMOSFET is suitable for quality assurance of beta sources for endovascular brachytherapy (EVBT). The homogeneity of the source is checked by measurements at five points (for the 60 mm source at 10, 20, 30, 40 and 50 mm) along the source train. The microMOSFET was then used to evaluate the influence of a common stent type (single layer stainless steel) on the dose distribution in water. The stent led to a dose inhomogeneity of +/-8.5%. Additionally the percentage depth dose curves with and without a stent were compared. The depth dose curves show good agreement which means that the stent does not change the beta spectrum significantly.     

Prospects for quantitative two-dimensional radiochromic film dosimetry for low dose-rate brachytherapy sources

Radiochromic film (RCF) has been shown to be a precise and accurate two-dimensional dosimeter for acute exposure radiation fields. However, "temporal history" mismatch between calibration and brachytherapy films due to RCF dose-rate effects could introduce potentially large uncertainties in low dose-rate (LDR) brachytherapy absolute dose measurement. This article presents a quantitative evaluation of the precision and accuracy of a laser scanner-based RCF-dosimetry system and the effect of the temporal history mismatch in LDR absolute dose measurement. MD-55-2 RCF was used to measure absolute dose for a low dose-rate 137Cs brachytherapy source using both single- and double-exposure techniques. Dose-measurement accuracy was evaluated by comparing RCF to Monte Carlo photon-transport simulation. The temporal history mismatch effect was investigated by examining dependence of RCF accuracy on irradiation-to-densitometry time interval. The predictions of the empirical cumulative dose superposition model (CDSM) were compared with measurements. For the double-exposure technique, the agreement between measurement and Monte Carlo simulation was better than 4% in the 3-60 Gy dose range with measurement precisions (coverage factor k = 1) of <2% and <6% for the doses greater or less than 3 Gy, respectively. The overall uncertainty (k = 1) of dose rate/air-kerma strength measurements achievable by this dosimetry system for a spatial resolution of 0.1 mm is less than 4% for doses greater than 5 Gy. The measured temporal history mismatch systematic error is about 1.8% for a 48 h postexposure time when using the double exposure technique and agrees with CDSM's prediction qualitatively. This work demonstrates that the model MD-55-2 RCF detector has the potential to support quantitative dose measurements about LDR brachytherapy sources with precision and accuracy better than that of previously described dosimeters. The impacts of this work on the future use of new type of RCF were also discussed.     

Neutron dosimetry for a general 252Cf brachytherapy source

This paper extends previous work to characterize neutron dosimetry in the vicinity of 252Cf brachytherapy sources. A general source is examined with an arbitrary length, diameter, and encapsulation using Monte Carlo methods. Fast neutron dosimetry and thermal neutron fluence rates were determined in a variety of clinically relevant media of varying dimensions. Applicator Tube, point source, high dose rate VariSource, and high dose rate muSelectron source geometries were analyzed. Fast neutron dosimetry was relatively independent of encapsulation thickness for an assortment of encapsulation materials less than 2 mm thick. Large variations in phantom size made minimal differences in the fast neutron dose close to the source. Specific source geometries were compared with dosimetry obtained from a simplified point model. The consequence of these results is a convenient means of accurately predicting clinical fast neutron dosimetry characteristics around a general 252Cf brachytherapy source in a variety of media without requiring neutron transport. Thermal neutron fluence rates were determined for a variety of source encapsulation materials, encapsulation thicknesses, and phantom sizes. At a distance of 3 cm from the source center, the thermal neutron fluence rate for a 30 cm diameter phantom was a 2.65 times greater than for a 10 cm diameter water phantom. These results demonstrate 252Cf thermal neutron fluence rate is relatively independent of encapsulation thickness and composition, yet highly dependent on hydrogen mass density and phantom size for phanta with diameters <30 cm.     

Electron capture radioactive sources for intravascular brachytherapy: a feasibility study

The feasibility of electron capture (EC) radionuclides as an alternative to the beta and high-energy gamma emitters presently in use for intravascular brachytherapy is investigated. A potential advantage of the low-energy x-ray radiation from EC isotopes may be an enhanced biological effectiveness with respect to the presently applied beta nuclides, but at the same time avoiding the shielding problems induced by the large penetrability of high-energy gamma rays. A survey considering the most important practical aspects such as dose delivery to the vessel walls in reasonable time spans, absorption properties, possible production of sources with the required specific activities and radiation safety reveals 71Ge as the most promising candidate.     

Characterization of miniature tissue-equivalent proportional counters for neutron radiotherapy applications

A miniature tissue-equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetric measurements in high-flux mixed fields. Counters with collecting volumes of 12.3 and 2.65 mm3 have been constructed using various tissue-equivalent wall materials, including those loaded with 10B for evaluation of the effects of the boron neutron capture reaction. These counters provide a measure of both the absorbed dose and associated radiation quality, allowing an assessment of the utility and relative effectiveness of various neutron radiotherapy techniques such as boron neutron capture therapy (BNCT), boron neutron capture enhanced fast neutron therapy (BNCEFNT) and intensity modulated neutron radiotherapy (IMNRT). An evaluation of the physical parameters affecting the measured microdosimetric spectrum, the gas multiplication characteristics and the measurement of absorbed dose is presented. In addition, important aspects of the calibration and low energy extrapolation techniques for the microdosimetric spectrum are provided.     

An absorbed dose to water standard for HDR 192Ir brachytherapy sources based on water calorimetry: numerical and experimental proof-of-principle

Water calorimetry is an established technique for absorbed dose to water measurements in external beams. In this paper, the feasibility of direct absorbed dose measurements for high dose rate (HDR) iridium-192 (192Ir) sources using water calorimetry is established. Feasibility is determined primarily by a balance between the need to obtain sufficient signal to perform a reproducible measurement, the effect of heat loss on the measured signal, and the positioning uncertainty affecting the source-detector distance. The heat conduction pattern generated in water by the Nucletron microSelectron-HDR 192Ir brachytherapy source was simulated using COMSOL MULTIPHYSICS software. Source heating due to radiation self-absorption was calculated using EGSnrcMP. A heat-loss correction k(c) was calculated as the ratio of the temperature rise under ideal conditions to temperature rise under realistic conditions. The calorimeter setup used a parallel-plate calorimeter vessel of 79 mm diameter and 1.12 mm thick front and rear glass windows located 24 mm apart. Absorbed dose was measured with two sources with nominal air kerma strengths of 38 000 and 21 000 U, at source-detector separations ranging from 24.7 to 27.6 mm and irradiation times of 36.0 to 80.0 s. The preliminary measured dose rate per unit air kerma strength of (0.502 +/- 0.007) microGy/(s U) compares well with the TG-43 derived 0.505 microGy/(s U). This work shows that combined dose uncertainties of significantly less than 5% can be achieved with only modest modifications of current water calorimetry techniques and instruments. This work forms the basis of a potential future absolute dose to water standard for HDR 192Ir brachytherapy.     

Gadolinium neutron capture therapy for brain tumors: a computer study.

A Monte Carlo computer study of the total dose distribution from neutrons and prompt gamma emissions (but excluding the contribution from conversion and Auger electrons) for gadolinium neutron capture therapy of brain tumors has been carried out in order to test the theoretic feasibility of this modality using commercially available magnetic resonance contrast media. The three-dimensional dose distribution calculations were performed in a spherical head phantom with a spherical tumor at the center. Potentially achievable gadolinium concentrations of 150 micrograms/g of tissue in tumor and 3 micrograms/g in normal tissue were assumed with enrichment to 79.9% gadolinium-157, as supplied by Oak Ridge National Laboratory. Irradiation was assumed to be with a 2-keV monoenergetic cylindrical epithermal neutron beam having a radius of 4 cm. The three-dimensional thermal neutron fluence resulting from the 2-keV beam propagation through the tissue was modeled. For a single neutron beam, the maximum dose is delivered within the tumor but the dose is very inhomogeneous across the tumor volume due to rapid decrease of thermal neutron fluence with depth. Two parallel opposed neutron beams deliver to the interface of normal and malignant tissue 70%-80% of the maximum dose received at the center of the tumor. To deliver an average tumor dose of 500 cGy in 10 min would require a 2-keV source neutrons number of 8.0 x 10(11) per s within the geometry of the beam.