Application of TEPC microdosimetry to boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a bimodal radiation therapy used primarily for highly malignant gliomas. Tissue-equivalent proportional counter (TEPC) microdosimetry has proven an ideal dosimetry technique for BNCT, facilitating accurate separation of the photon and neutron absorbed dose components, assessment of radiation quality and measurement of the BNC dose. A miniature dual-TEPC system has been constructed to facilitate microdosimetry measurements with excellent spatial resolution in high-flux clinical neutron capture therapy beams. A 10B-loaded TEPC allows direct measurement of the secondary charged particle spectrum resulting from the BNC reaction. A matching TEPC fabricated from brain-tissue-equivalent plastic allows evaluation of secondary charged particle spectra from photon and neutron interactions in normal brain tissue. Microdosimetric measurements performed in clinical BNCT beams using these novel miniature TEPCs are presented, and the advantages of this technique for such applications are discussed.     

Boron microquantification in oral muscosa and skin following administration of a neutron capture therapy agent

Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronophenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the 10B(n, alpha)7Li reaction products is very short, 10-14 microns combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of 10B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced etched track autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the 10B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration.     

Nuclear fragmentation and the number of particle tracks in tissue

For high energy nuclei, the number of particle tracks per cell is modified by local nuclear reactions that occur, with large fluctuations expected for heavy ion tracks. Cells near the interaction site of a reaction will experience a much higher number of tracks than estimated by the average fluence. Two types of reaction products are possible and occur in coincidence; projectile fragments, which generally have smaller charge and similar velocity to that of the projectile, and target fragments, which are produced from the fragmentation of the nuclei of water atoms or other cellular constituents with low velocity. In order to understand the role of fragmentation in biological damage a new model of human tissue irradiated by heavy ions was developed. A box of the tissue is modelled with periodic boundary conditions imposed, which extrapolates the technique to macroscopic volumes of tissue. The cross sections for projectile and target fragmentation products are taken from the quantum multiple scattering fragmentation code previously developed at NASA Johnson Space Center. Statistics of fragmentation pathways occurring in a cell monolayer, as well as in a small volume of 10 x 10 x 10 cells are given. A discussion on approaches to extend the model to describe spatial distributions of inactivated or other cell damage types, as well as highly organised tissues of multiple cell types, is presented.     

Radiation quality of photons in small and large receptors--a microdosimetric analysis

The quality of different photon radiations in small and largereceptors is assessed in terms of microdosimetry. Monte Carlosimulations are performed for the electrons released by photons.To represent the case of a small receptor, only electrons releasedby the non-degraded incident photons are tracked. For a largereceptor, all electrons released in the complete degradationprocess are followed. Dose averaged values, y_D, of the linealenergy are derived from the simulated tracks for monoenergeticphotons from 10 keV to 2 MeV. In microdosimetry, the dose meanlineal energy is the major parameter of radiation quality. Theresults demonstrate distinct differences in radiation qualitybetween high-energy gamma rays and conventional X rays thatare present not just in small cell samples but also in largereceptors, such as the human body. The values of y_D suggestthat, for both small and large receptors, conventional X raysshould be about twice as effective as gamma rays from ⁶⁰Co.     

An approach to Monte Carlo simulation of low-energy electron and photon interactions in air

In this paper we present an approach to an energy deposition model for low energy (10 eV–10 keV) photons and electrons. The model is based on Monte Carlo simulations of the tracks and energy loss resulting from single electron scattering events with the constituent molecules of air, namely N₂ and O₂. The simulation code is based on the Geant4 toolkit. The original physics in Geant4 low-energy processes for photon interactions was used for the incoming photons and secondary X- and gamma-rays, from energies below 1–10 keV. Two new electron interaction processes were developed,and both of them were considered as discrete processes. The new implemented physics is based on experimental cross-sections for elastic and inelastic scattering, complemented with theoretical calculations. Ionization is treated as a subprocess of the inelastic process. The implementation of the new processes in the standard Geant4 frame is considered. Validation tests and comparison with other Monte Carlo results are discussed. The current limitations of this version of the code are also outlined. The code can be of interest in areas where energy deposition at microscopic level is crucial, such as microdosimetry.     

Classical microdosimetry in radiation protection dosimetry and monitoring

Classical microdosimetry concerns the measurement and analysis of the spectrum of radiation energy deposition events in simulated microscopic tissue-equivalent sites. Over the past three decades, classical microdosimetry has been extensively applied for the direct measurement of dosimetric quantities, such as the ambient dose equivalent, and for the spectroscopic properties of tissue-equivalent proportional counters that have led to methods of mixed-field analysis and particle identification. This paper reviews some of the special applications of classical microdosimetry such as the determination of kerma coefficients, differential dosimetry and aviation dosimetry. Also reviewed are some of the technological innovations related to the application of microdosimetry in operational health physics and in particular the development of multi-element proportional counters and detectors based on gas microstrip technology.     

Charge transfer and ionisation by intermediate-energy heavy ions

The use of heavy ion beams for microbeam studies of mammalian cell response leads to a need to better understand interaction cross sections for collisions of heavy ions with tissue constituents. For ion energies of a few MeV u(-1) or less, ions capture electrons from the media in which they travel and undergo subsequent interactions as partially 'dressed' ions. For example, 16 MeV fluorine ions have an equilibrium charge of 7(+), 32 MeV sulphur ions have an equilibrium charge of approximately 11(+), and as the ion energies decrease the equilibrium charge decreases dramatically. Data for interactions of partially dressed ions are extremely rare, making it difficult to estimate microscopic patterns of energy deposition leading to damage to cellular components. Such estimates, normally obtained by Monte Carlo track structure simulations, require a comprehensive database of differential and total ionisation cross sections as well as charge transfer cross sections. To provide information for track simulation, measurement of total ionisation cross sections have been initiated at East Carolina University using the recoil ion time-of-flight method that also yields cross sections for multiple ionisation processes and charge transfer cross sections; multiple ionisation is prevalent for heavy ion interactions. In addition, measurements of differential ionisation cross sections needed for Monte Carlo simulation of detailed event-by-event particle tracks are under way. Differential, total and multiple ionisation cross sections and electron capture and loss cross sections measured for C(+) ions with energies of 100 and 200 keV u(-1) are described.     

A database of frequency distributions of energy depositions in small-size targets by electrons and ions

Linear energy transfer (LET) is an average quantity, which cannot display the stochastics of the interactions of radiation tracks in the target volume. For this reason, microdosimetry distributions have been defined to overcome the LET shortcomings. In this paper, model calculations of frequency distributions for energy depositions in nanometre size targets, diameters 1-100 nm, and for a 1 μm diameter wall-less TEPC, for electrons, protons, alpha particles and carbon ions are reported. Frequency distributions for energy depositions in small-size targets with dimensions similar to those of biological molecules are useful for modelling and calculations of DNA damage. Monte Carlo track structure codes KURBUC and PITS99 were used to generate tracks of primary electrons 10 eV to 1 MeV, and ions 1 keV μm(-1) to 300 MeV μm(-1) energies. Distribution of absolute frequencies of energy depositions in volumes with diameters of 1-100 nm randomly positioned in unit density water irradiated with 1 Gy of the given radiation was obtained. Data are presented for frequency of energy depositions and microdosimetry quantities including mean lineal energy, dose mean lineal energy, frequency mean specific energy and dose mean specific energy. The modelling and calculations presented in this work are useful for characterisation of the quality of radiation beam in biophysical studies and in radiation therapy.     

Cluster-based centralized data fusion for tracking maneuvering targets using interacting multiple model algorithm

The interacting multiple model (IMM) algorithm has proved to be useful in tracking maneuvering targets. Tracking accuracy can be further improved using data fusion. Tracking of multiple targets using multiple sensors and fusing them at a central site using centralized architecture involves communication of large volumes of measurements to a common site. This results in heavy processing requirement at the central site. Moreover, track updates have to be obtained in the fusion centre before the next measurement arrives. For solving this computational complexity, a cluster-based parallel processing solution is presented in this paper. In this scheme, measurements are sent to the data fusion centre where the measurements are partitioned and given to the slave processors in the cluster. The slave processors use the IMM algorithm to get accurate updates of the tracks. The master processor collects the updated tracks and performs data fusion using ‘weight decision approach’. The improvement in the computation time using clusters in the data fusion centre is presented in this paper     

Microdosimetric study for interpretation of outcomes from boron neutron capture therapy clinical trials

Boron neutron capture therapy is a brachyradiotherapy utilizing the (10)B(n,alpha)(7)Li reaction that has been used to treat glioblastoma multiforme (GBM), melanoma and colon carcinoma liver metastases. GBM clinical trials resulted in modestly improved life expectancies compared with conventional therapies. Early results trials focused on malignant melanoma and colon carcinoma provide dramatically better results. Macrodosimetry cannot explain these apparent differences. The dichotomy can only be understood using microdosimetry techniques. A computer program has been created to provide an improved tissue model. This model permits the dose in each cell's cytoplasm, nucleus, and the interstitium to be calculated for ellipsoidal cells placed in either random or ordered locations. The nuclei can be centered or eccentric. The new model provides insight into the micro level for differences in the trials. The differences arise from the tissue's cellular geometry and the effects of neighboring cells. These results help to explain the observed clinical outcomes.     

Charge collection imaging of a monolithic DeltaE-E telescope for radiation protection applications

The development of microdosimeters and particle telescopes is important for risk assessment in space and aviation applications. The charge collection properties of a monolithic particle telescope, suitable for both microdosimetry and fluence based approaches, were studied using an ion microprobe.     

Solid state microdosimetry in hadron therapy

A report of recent developments in silicon microdosimetry is presented. SOI based microdosemeters have shown promise as a viable alternative to traditional tissue-equivalent proportional counters. The application of these silicon microdosemeters to such radiation therapy modalities as boron neutron capture therapy (BNCT), boron neutron capture synovectomy (BNCS), proton therapy (PT), and fast neutron therapy (FNT) has been performed. Several shortcomings of the current silicon microdosemeter were identified and will be taken into account in the design of a second-generation device.     

Techniques for radiation measurements: microdosimetry and dosimetry

Experimental microdosimetry is concerned with the determination of radiation quality and how this can be specified in terms of the distribution of energy deposition arising from the interaction of a radiation field with a particular target site. This paper discusses various techniques that have been developed to measure radiation energy deposition over the three orders of magnitude of site-size; nanometer, micrometer and millimetre, which radiation biology suggests is required to fully account for radiation quality. Inevitably, much of the discussion will concern the use of tissue-equivalent proportional counters and variants of this device, but other technologies that have been studied, or are under development, for their potential in experimental microdosimetry are also covered. Through an examination of some of the quantities used in radiation metrology and dosimetry the natural link with microdosimetric techniques will be shown and the particular benefits of using microdosimetric methods for dosimetry illustrated.     

Imaging of microscopic features of charged particle tracks in a low-pressure gas

An imaging system for measuring the spatial distribution of charged particle tracks in a low-pressure gas is presented. The method is based on an optically read out time projection chamber. Results of experiments with fast heavy ions are shown.     

Design and performance of the SLD vertex detector: a 307 Mpixel tracking system

This paper describes the design, construction, and initial operation of SLD's upgraded vertex detector which comprises 96 two-dimensional charge-coupled devices (CCDs) with a total of 307 Mpixel. Each pixel functions as an independent particle detecting element, providing space point measurements of charged particle tracks with a typical precision of 4 μm in each co-ordinate. The CCDs are arranged in three concentric cylinders just outside the beam-pipe which surrounds the e⁺e⁻ collision point of the SLAC Linear Collider (SLC). The detector is a powerful tool for distinguishing displaced vertex tracks, produced by decay in flight of heavy flavour hadrons or tau leptons, from tracks produced at the primary event vertex. The requirements for this detector include a very low mass structure (to minimize multiple scattering) both for mechanical support and to provide signal paths for the CCDs; operation at low temperature with a high degree of mechanical stability; and high speed CCD readout, signal processing, and data sparsification. The lessons learned in achieving these goals should be useful for the construction of large arrays of CCDs or active pixel devices in the future in a number of areas of science and technology.     

Hypervelocity impact testing of micrometeorite capture cells in conjunction with a PVDF thin-film velocity/trajectory sensor and a simple plasma velocity detector

Five different small particle capture cell designs were evaluated for their ability to capture fragments and residue from 10–200 μm diameter glass projectiles and oblong olivine crystals impacting at 1–15 km/s in sufficient quantity for chemical and isotopic analyses. Aluminum multi-foils (0.1–100 μm thick with ≈10, 000 and 1800 μm spacing), foil covered germanium crystals, and 0.50 and 0.120 g/cm³ Aerogels, were positioned behind either multi-film (1.4–6.0 μm thick) polyvinylidene fluoride (PVDF) velocity/trajectory sensor devices of a simple wire-grid plasma velocity detector. All capture cells collected significant amounts of impactor debris behind the PVDF sensors from nominal 100 μm diameter glass projectiles and olivine crystals which struck the sensor at velocities up to 6.4 km/s. At velocities >8 km/s little or no debris penetrated the second PVDF film. Results were incolsive for velocities between 6.5 and 8 km/s. Plasma detector results showed identifiable impactor residue on Al foils for velocities up to 8.7 km/s and impact tracks with apparent debris imbedded in the Aerogels for velocities up to 12.7 km/s. Maximum foil penetration of glass spheres and olivine crystals were the same, but more particulate debris was associated with olivine crystal ipacts versus glass impacts. Foil spacing beyond one particle diameter had no effect on total penetration. Aerogels are identified as a capture cell media that warrants further investigation. The Al multi-foil capture cell with 100 μm net spacers is identified as the most effective of the other designs and offers the advantages of compact structure, low secondary ejecta from impacts, and easy recovery of impactor debris for analysis.     

Preliminary design of a Gd-NCT neutron beam based on compact D-T neutron source

Gadolinium has been recently proposed, as neutron capture agent in NCT (Neutron Capture Therapy), due to both the nuclide high neutron capture cross section, and the remarkable selective uptake inside tumour tissue that Gd-loaded compounds, can provide. When a neutron external source is supplied, different Gd nuclear reactions, and the generated Auger electrons in particular, cause a high local energy deposition, which results in a tumour cell inactivation. Preliminary micro- as well as macrodosimetric Monte Carlo computational investigations show that the tumour-to-healthy tissue biological damage ratio is in close relation to the neutron beam energy spectrum. The results points out that the optimum neutron spectrum, to be used for Gd-NCT, seems to lie in the 1 to 10 keV energy range. In order to 'tailor' such spectra, an original, accelerator-driven, neutron source and spectrum shaping assembly for hospital-based Gd-NCT are presented and preliminary results are reported.     

Hot wire chemical vapour deposition (HWCVD) of boron carbide thin films from ortho-carborane for neutron detection application

Detection of neutrons is possible if suitable converters such as Li, LiF or ¹⁰B in the form of thin films are used along with the semiconductor device. The use of boron (¹⁰B) in some host matrix as a neutron detector is attractive due to its large neutron capture cross-section. Boron carbide (BC) films are deposited on silicon substrates by HWCVD technique using solid ortho-carborane (o-C₂B₁₀H₁₂) precursor with argon as carrier gas. The films contain ¹⁰B required for neutron detection as confirmed by the Secondary Ion Mass Spectroscopy. Variations in its structure as well as the chemical bonding configurations using Fourier Transform Infra-Red, Raman and X-ray diffraction spectroscopy have been studied.     

Calibration of the borated ion chamber at NIST reactor thermal column

In boron neutron capture therapy and boron neutron capture enhanced fast neutron therapy, the absorbed dose of tissue due to the boron neutron capture reaction is difficult to measure directly. This dose can be computed from the measured thermal neutron fluence rate and the (10)B concentration at the site of interest. A borated tissue-equivalent (TE) ion chamber can be used to directly measure the boron dose in a phantom under irradiation by a neutron beam. Fermilab has two Exradin 0.5 cm(3) Spokas thimble TE ion chambers, one loaded with boron, available for such measurements. At the Fermilab Neutron Therapy Facility, these ion chambers are generally used with air as the filling gas. Since alpha particles and lithium ions from the (10)B(n,alpha)(7)Li reactions have very short ranges in air, the Bragg-Gray principle may not be satisfied for the borated TE ion chamber. A calibration method is described in this paper for the determination of boron capture dose using paired ion chambers. The two TE ion chambers were calibrated in the thermal column of the National Institute of Standards and Technology (NIST) research reactor. The borated TE ion chamber is loaded with 1,000 ppm of natural boron (184 ppm of (10)B). The NIST thermal column has a cadmium ratio of greater than 400 as determined by gold activation. The thermal neutron fluence rate during the calibration was determined using a NIST fission chamber to an accuracy of 5.1%. The chambers were calibrated at two different thermal neutron fluence rates: 5.11 x 10(6) and 4.46 x 10(7)n cm(-2) s(-1). The non-borated ion chamber reading was used to subtract collected charge not due to boron neutron capture reactions. An optically thick lithium slab was used to attenuate the thermal neutrons from the neutron beam port so the responses of the chambers could be corrected for fast neutrons and gamma rays in the beam. The calibration factor of the borated ion chamber was determined to be 1.83 x 10(9) +/- 5.5% (+/- 1sigma) n cm(-2) per nC at standard temperature and pressure condition.