Measured microdosimetric spectra and therapeutic potential of boron neutron capture enhancement of 252Cf brachytherapy.

Californium-252 is a neutron-emitting radioisotope used as a brachytherapy source for radioresistant tumors. Presented here are microdosimetric spectra measured as a function of simulated site diameter and distance from applicator tube 252Cf sources. These spectra were measured using miniature tissue-equivalent proportional counters (TEPCs). An investigation of the clinical potential of boron neutron capture (BNC) enhancement of 252Cf brachytherapy is also provided. The absorbed dose from the BNC reaction was measured using a boron-loaded miniature TEPC. Measured neutron, photon and BNC absorbed dose components are provided as a function of distance from the source. In general, the absorbed dose results show good agreement with results from other measurement techniques. A concomitant boost to 252Cf brachytherapy may be provided through the use of the BNC reaction. The potential magnitude of this BNC enhancement increases with increasing distance from the source and is capable of providing a therapeutic gain greater than 30% at a distance of 5 cm from the source, assuming currently achievable boron concentrations.

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.

Miniature tissue-equivalent proportional counters for BNCT and BNCEFNT dosimetry.

A dual miniature tissue-equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetry for Boron Neutron Capture Therapy (BNCT). This system has been designed specifically to allow the analysis of the single event charged particle spectrum in phantom in high intensity BNCT beams and to provide this microdosimetric information with excellent spatial resolution. Paired A-150 and 10B-loaded A-150 TEPCs with 12.3 mm3 collecting volumes have been constructed. These TEPCs allow more accurate neutron dosimetry than current techniques, offer a direct measure of the boron neutron capture dose, and provide a framework for predicting the biological effectiveness of the absorbed dose. Design aspects and characterization of these detectors are reviewed, along with an exposition of the advantages of microdosimetry using these detectors over conventional dosimetry methods. In addition, the utility of this technique for boron neutron capture enhancement of fast neutron therapy (BNCEFNT) is discussed.

A conducting plastic simulating brain tissue.

A new conducting plastic has been composed which accurately simulates the photon and neutron absorption properties of brain tissue. This tissue-equivalent (TE) plastic was formulated to match the hydrogen and nitrogen constituents recommended by ICRU Report #44 for brain tissue. Its development was initiated by the inability of muscle tissue-equivalent plastic to closely approximate brain tissue with respect to low-energy neutron interactions. This new plastic is particularly useful as an electrode in TE dosimetry devices for boron neutron capture therapy (BNCT), which utilizes low-energy neutrons for radiotherapy of the brain. Absorbed dose measurements in a clinical BNCT beam using a proportional counter constructed from this TE plastic show good agreement with Monte Carlo calculations.

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.

Paired Mg and Mg(B) ionization chambers for the measurement of boron neutron capture dose in neutron beams.

The use of the boron neutron capture (BNC) reaction to provide a dose enhancement in fast neutron therapy is currently under investigation at the Gershenson Radiation Oncology Center of Harper Hospital in Detroit, MI. The implementation of this treatment modality presents unique challenges in dosimetry. In addition to the measurement of photon and neutron doses in the mixed field, a measure of the thermal neutron flux and the associated boron neutron capture dose throughout the treatment volume is desired. A pair of small-volume magnesium ionization chambers has been constructed with the aim of providing this information. One of the chambers, denoted the Mg(B) chamber, is lined with a boron-loaded foil. The ionization response of this chamber has been calibrated in terms of BNC dose per ppm loading of 10B. These paired chambers can be used to map the local BNC response in neutron beams. From this data and an estimation of the boron concentration in the tumor and normal tissue, the boron neutron capture enhancement may be evaluated.

Dosimetry of the boron neutron capture reaction for BNCT and BNCEFNT.

The use of paired proportional counters, constructed from A-150 tissue equivalent plastic (TEP) and A-150 TEP loaded with an appropriate amount of 10B (50 to 200 ppm), for the dosimetry of the boron neutron capture reaction has been investigated for several years at the Gershenson Radiation Oncology Center. This method has been used for determining the dose components (fast neutron, gamma ray and boron capture product dose) in both Boron Neutron Capture Therapy (BNCT) beams and in beams proposed for boron neutron capture enhancement of fast neutron therapy (BNCEFNT). A disadvantage of this method, when standard 1/2" diameter Rossi type proportional counters are used, is that the beam intensity must be relatively low in order to avoid saturation effects (pulse pile-up) in the counter. This is a major problem if measurements are to be made in a reactor beam, since reducing the beam intensity generally results in a change in the neutron spectrum. In order to overcome this problem, miniature cylindrical proportional counters have been developed which may be used in high intensity beams. The operational characteristics of these counters are compared with the standard 1/2" spherical counters. A further disadvantage of proportional counters is the relatively long time it takes to collect data, particularly if detailed information (depth-dose curves and beam profiles) is required. This problem could be overcome by using a set of ionization chambers (an A-150 TEP chamber, a Mg chamber and a Mg chamber with a 25 microns boron loaded inner wall) which can be scanned in a water phantom. After calibration against the paired proportional counters it should be possible to extract the fast neutron, gamma ray and boron neutron capture product doses from measurements made with these three ionization chambers. A set of such chambers has been used to make preliminary measurements in a fast neutron beam and the results of these measurements are presented.

Experimental determination of the thermal neutron flux around two different types of high intensity 252Cf sources.

The application of neutron emitting radioisotopes in brachytherapy facilitates the use of the higher biological effectiveness of neutrons compared to photons in treating some cancers. Different types of high intensity 252Cf sources are in use for the treatment of different cancers. To improve the therapy of bulky tumors the dose can be augmented by the additional use of the boron capture reaction of thermal neutrons. This requires information about the thermal neutron dose component around the Cf source. In this work, a Mg/Ar-ionization chamber internally coated with 10B was used to measure the thermal neutrons. These measurements were performed on two different 252Cf sources, one in use in the Gershenson Radiation Oncology Center at Harper Hospital in Detroit, MI, and one at the University Hospital of Chiang Mai in Chiang Mai, Thailand. The results of these measurements are compared and indicate that the differences in the construction of the sources influence the thermal dose component.

Direct determination of kerma for a d(48.5) + Be therapy beam.

An experimental determination of the neutron kerma ratio between muscle tissue and A-150 plastic was performed at the newly commissioned d(48.5)+ Be therapy facility in Detroit. Low-pressure proportional counters with separate walls made from A-150 plastic, graphite, zirconium oxide and zirconium served to measure ionization yield spectra. The absorbed dose in the wall of each counter was determined and rendered the A-150 and carbon kerma directly, whilst that for oxygen was deduced from differences between the matched metal oxide and metal pair. This enabled the evaluation of an effective kerma ratio as a function of radiation field size and hydrogenous filtration. Although filtration was observed to harden the beam, the application of a single kerma ratio for the various irradiation conditions investigated was found to be appropriate. A neutron kerma ratio of 0.90+/-0.03 was assessed for the Detroit facility, which is lower at the 1sigma level than the 0.95 currently recommended in the dosimetry protocol for high-energy neutron beams.

Measurement of the neutron sensitivity of TLD-300 irradiated in a tissue equivalent phantom by d(48.5) + Be neutrons.

The neutron sensitivities of the total response (kT) as well as of separate peaks 3 (k3) and 5 (k5) on the glow curve were measured for CaF2:Tm (TLD-300) thermoluminescent dosimeters. The TLD-300 were encapsulated in A-150 TE plastic and located at different depths in the water phantom. The phantom was irradiated with neutrons produced by the d(48.5) + Be reaction at the superconducting cyclotron of the Gershenson Radiation Oncology Center at Harper Hospital. A set of measurements, based on the use of a TE ionization chamber and Geiger-Müller (GM) counter was used to measure the neutron (Dn) and gamma (D gamma) dose at these locations. The neutron sensitivities of the TLDs were thus derived by comparison with the results obtained with the twin detector method. The average neutron sensitivities relative to gamma of the total response and the responses of single peaks 3 or 5 are 0.215 +/- 0.016, 0.126 +/- 0.010, and 0.357 +/- 0.014, respectively. A linear relationship was found between the ratio of the areas under peak 3 to that under peak 5 and the ratio of the gamma dose to the total dose.

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.

A measurement of the fast-neutron sensitivity of a Geiger-Müller detector in the pulsed neutron beam from a superconducting cyclotron.

The kU value of a commercially available miniature energy compensated Geiger-Müller (GM) detector has been determined using the modified lead attenuation method of Hough. The measurements were made in a d(48.5)-Be neutron beam produced by the superconducting cyclotron based neutron therapy facility at Harper Hospital. The unique problems associated with making measurements in a 2 ms duration pulsed beam with a 20% duty cycle are discussed. The beam monitoring system, which allows the beam pulse shape at low beam intensities to be measured, is described. By gating the GM output with a discriminator pulse derived from the beam pulse shape, the gamma-ray count rates and dead-time corrections within the 2 ms pulse and between pulses can be measured separately. The kU value of (0.0245 +/- 0.0015) determined for this GM detector is consistent with the values measured by other workers with identical and similar detectors in neutron beams with comparable, but not identical, neutron spectra.

A dosimetry system for boron neutron capture therapy based on the dual counter microdosimetric technique.

A dosimetric technique based on proportional counter microdosimetry has been developed for the dosimetry of mixed radiation fields employed in boron neutron capture therapy (BNCT). The technique has been successfully used to measure the gamma, fast neutron and the boron dose rates in the mixed radiation field from a 252Cf source. The measured fast neutron and boron dose rates are in good agreement with the calculations and the measurements reported by other researchers. A systematic discrepancy is observed in the gamma dose rate measurements, with the present measurements being approximately 35% lower than those reported elsewhere.