Jacquelyn C. Yanch

MIXED FIELD DOSIMETRY OF EPITHERMAL NEUTRON BEAMS FOR BORON NEUTRON CAPTURE THERAPY AT THE MITR-II RESEARCH REACTOR

During the past several years, there has been growing interest in Boron Neutron Capture Therapy (BNCT) using epithermal neutron beams. The dosimetry of these beams is challenging. The incident beam is comprised mostly of epithermal neutrons, but there is some contamination from photons and fast neutrons. Within the patient, the neutron spectrum changes rapidly as the incident epithermal neutrons scatter and thermalize, and a photon field is generated from neutron capture in hydrogen. In this paper, a method to determine the doses from thermal and fast neutrons, photons, and the B-10(n, alpha)Li-7 reaction is presented. The photon and fast neutron doses are measured with ionization chambers, in realistic phantoms, using the dual chamber technique. The thermal neutron flux is measured with gold foils using the cadmium difference technique, the thermal neutron and B-10 doses are determined by the kerma factor method. Representative results are presented for a unilateral irradiation of the head. Sources of error in the method as applied to BNCT dosimetry, and the uncertainties in the calculated doses are discussed.

Accelerator-based Epithermal Neutron Sources for Boron Neutron Capture Therapy of Brain Tumors

SummaryThis paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (∼

Accelerator‐based epithermal neutron beam design for neutron capture therapy

1.5 M) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (∼10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and the use of microchannels have emerged as viable target cooling options. Neutron fields for reactor-based neutron sources provide an obvious basis of comparison for ABNS field quality. This paper compares Monte Carlo calculations of neutron field quality for an ABNS and an idealized standard reactor neutron field (ISRNF). The comparison shows that with lithium as a target, an ABNS can create a neutron field with a field quality that is significantly better (by a factor of ∼1.2, as judged by the relative biological effectiveness (RBE)-dose that can be delivered to a tumor at a depth of 6 cm) than that for the ISRNF. Also, for a beam current of 10 mA, the treatment time is calculated to be reasonable (∼30 min) for the boron concentrations that have been assumed.

Increased Radiation Dose to Overweight and Obese Patients from Radiographic Examinations

Recent interest in the production of epithermal neutrons for use in boron neutron capture therapy (BNCT) has promoted an investigation into the feasibility of generating such neutrons with a high current proton accelerator. Energetic protons (2.5 MeV) on a 7Li target produce a spectrum of neutrons with maximum energy of roughly 800 keV. A number of combinations of D2O moderator, lead reflector, 6Li thermal neutron filtration, and D2O/6Li shielding will result in a useful epithermal flux of 1.6 x 10(8) n/s at the patient position. The neutron beam is capable of delivering 3000 RBE-cGy to a tumor at a depth of 7.5 cm in a total treatment time of 60-93 min (depending on RBE values used and based on a 24-cm diameter x 19-cm length D2O moderator). Treatment of deeper tumors with therapeutic advantage would also be possible. Maximum advantage depths (RBE weighted) of 8.2-9.2 (again depending on RBE values and precise moderator configuration) are obtained in a right-circular cylindrical phantom composed of brain-equivalent material with an advantage ratio of 4.7-6.3. A tandem cascade accelerator (TCA), designed and constructed at Science Research Laboratory (SRL) in Somerville MA, can provide the required proton beam parameters for BNCT of deep-seated tumors. An optimized configuration of materials required to shift the accelerator neutron spectrum down to therapeutically useful energies has been designed using Monte Carlo simulation in the Whitaker College Biomedical Imaging and Computation Laboratory at MIT. Actual construction of the moderator/reflector assembly is currently underway.

Measurement of the thick-target 9Be(p, n) neutron energy spectra

PURPOSE To estimate the increase in effective radiation dose from diagnostic x-rays for overweight and obese adult patients, as compared with the effective dose for lean reference phantoms. MATERIALS AND METHODS Relative effective radiation doses (E/E(0)) for the acquisition of chest and abdominal radiographs were calculated by using Monte Carlo computer simulations of effective doses delivered to adult phantoms with (E) and without (E(0)) subcutaneous adipose tissue added to the torso for five fat distributions. Total (anterior plus posterior) fat thicknesses ranged from 0 to 38 cm. RESULTS For 30 cm of additional fat, E/E(0) values for 120-kVp chest and 80-kVp abdomen radiographs ranged from approximately 2 to 31 and 2 to 83 for male patients, respectively, and from 2 to 45 and 2 to 76 for female patients, respectively, depending on the type of fat distribution and patient orientation in the x-ray beam (anteroposterior or posteroanterior). Orienting the patient such that the thinnest fat layer was facing away from the x-ray tube minimized E/E(0), which was well approximated by using the formula E/E(0) = [B(t)/B(0)] x exp(kt(DF)), where B(t) and B(0) are the antiscatter grid Bucky factors for patient thicknesses of t and t = 20 cm, respectively; k, a constant; and t(DF), the distal (beam exit) fat layer thickness. Reductions in E/E(0) reached 14% and 20% for the thickest phantoms when x-ray tube voltages were increased by 10 and 20 kVp, respectively, for abdominal radiography in the male phantom. CONCLUSION Effective doses from radiographic examinations in the extremely obese can exceed 100 mSv from only a small number of abdominal examinations and should be minimized to the extent possible and monitored. Exponential dose increases for increased subcutaneous fat thicknesses can be reduced substantially by positioning the patient so that the thinnest fat layer (anterior or posterior) is closest to the image receptor. Increasing the tube voltage also reduces the dose-but to a much smaller extent.

A Monte Carlo investigation of the dosimetric properties of monoenergetic neutron beams for neutron capture therapy.

Abstract The thick-target neutron energy spectra of the 9Be(p,n) reaction were measured at several angles for proton-bombarding energies of 3.0, 3.4, 3.7, 4.0, and 5.0 MeV. Time-of-flight techniques were used to determine the neutron energy spectra and to discriminate against background radiation. By using lithium-loaded glass scintillators and low proton pulse rate frequency, the neutron spectra have been determined at energies as low as 70 keV. The detectors were calibrated for efficiency using the neutron spectrum of the Al(d,n) reaction, which was accurately measured using fission chamber detectors.

Monte Carlo Based Dosimetry and Treatment Planning for Neutron Capture Therapy of Brain Tumors

A Monte Carlo simulation study has been carried out to investigate the suitability of neutron beams of various energies for therapeutic efficacy in boron neutron capture therapy. The dosimetric properties of unidirectional, monoenergetic neutron beams of varying diameters in two different phantoms (a right-circular cylinder and an ellipsoid) made of brain-equivalent material were examined. The source diameter was varied from 0.0 to 20.0 cm; neutron energies ranged from 0.025 eV up to 800 keV, the maximum neutron energy generated by a tandem cascade accelerator using 2.5-MeV protons in a 7Li(p,n)7Be reaction. Such a device is currently under investigation for use as a neutron source for boron neutron capture therapy. The simulation studies indicate that the maximum effective treatment depth (advantage depth) in the brain is 10.0 cm and is obtainable with a 10-keV neutron beam. A useful range of energies, defined as those neutron energies capable of effectively treating to a depth of 7 cm in brain tissue, is found to be 4.0 eV to 40.0 keV. Beam size is shown not to affect advantage depth as long as the entire phantom volume is used in determining this depth. Dose distribution in directions parallel to and perpendicular to the beam direction are shown to illustrate this phenomenon graphically as well as to illustrate the differences in advantage depth and advantage ratio and the contribution of individual dose components to tumor dose caused by the geometric differences in phantom shape.

Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice after Continuous Irradiation at ~ 400-Fold Natural Background Radiation

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described.

Boron neutron capture therapy and radiation synovectomy research at the Massachusetts Institute of Technology Research Reactor

Background: In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. Objectives: DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. Methods: We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. Results: We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break–induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. Conclusions: These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Monte Carlo methods of neutron beam design for neutron capture therapy at the MIT Research Reactor (MITR-II).

In this paper, current research in boron neutron capture therapy (BNCT) and radiation synovectomy at the Massachusetts Institute of Technology Research Reactor is reviewed. In the last few years, major emphasis has been placed on the development of BNCT primarily for treatment of brain tumors. This has required a concerted effort in epithermal beam design and construction as well as the development of analytical capabilities for {sup 10}B analysis and patient treatment planning. Prompt gamma analysis and high-resolution track-etch autoradiography have been developed to meet the needs, respectively, for accurate bulk analysis and for quantitative imaging of {sup 10}B in tissue at subcellular resolutions. Monte Carlo-based treatment planning codes have been developed to ensure optimized and individualized patient treatments. In addition, the development of radiation synovectomy as an alternative therapy to surgical intervention is joints that are affected by rheumatoid arthritis is described.