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F J Wheeler

Publications and source records attributed to F J Wheeler.

14 recordsLinked to original sources
PubMed1999

Boron neutron capture therapy (BNCT): implications of neutron beam and boron compound characteristics.

The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal-neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well-characterized epithermal-neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR-1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p-Boronophenylaline Fructose (BPA-F) and a hypothetical next-generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal-neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy-tissue tolerance and a reduction in the hydrogen-recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR-1 beam has the better quality (lower hydrogen-recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR-1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully optimized.

Biophysics↗
PubMed1998

The compound factor of the 10B(n,alpha)7Li reaction from borocaptate sodium and the relative biological effectiveness of recoil protons for induction of brain damage in boron neutron capture therapy.

To make clinical trials of boron neutron capture therapy safe for patients, it is necessary to know the relative biological effectiveness (RBE) of the radiation components and the compound factor of the boron carrier to be used. Here a method is derived to determine the RBE of recoil protons and the compound factor of compounds from in vivo experiments with different concentrations of boron. The method uses a simultaneous fit of both these parameters to all experimental data. This method is applied to the studies of tolerance of healthy tissue in dogs at the High Flux Reactor in Petten, The Netherlands. The RBE for the recoil protons generated by the neutrons present in the epithermal neutron beam [together with the RBE of the protons from the 14N(n,p)14C reaction] for induction of severe neurological symptoms was found to be 3.93+/-0.43 (95% confidence limits 3.06-4.79), and 2.33+/-0.14 (2.04-2.61) for induction of changes detectable by magnetic resonance imaging. The compound factor for Na2B12H11SH in brain tissue, using severe neurological symptoms as end point, was determined to be 0.37+/-0.06 (95% confidence limits 0.24-0.50). For changes detectable by magnetic resonance imaging, the value was found to be 0.65+/-0.04 (0.58-0.73).

Animals↗
PubMed1997

Computational dosimetry and treatment planning for boron neutron capture therapy.

The technology for computational dosimetry and treatment planning for Boron Neutron Capture Therapy (BNCT) has advanced significantly over the past few years. Because of the more complex nature of the problem, the computational methods that work well for treatment planning in photon radiotherapy are not applicable to BNCT. The necessary methods have, however, been developed and have been successfully employed both for research applications as well as human trials, although further improvements in speed are needed for routine clinical applications. Computational geometry for BNCT applications can be constructed directly from tomographic medical imagery and computed radiation dose distributions can be readily displayed in formats that are familiar to the radiotherapy community.

Animals↗
PubMed1996

An improved neutron collimator for brain tumor irradiations in clinical boron neutron capture therapy.

To improve beam penetration into a head allowing the treatment of deeper seated tumors, two neutron collimators were built sequentially and tested for use in the clinical boron neutron capture therapy (BNCT) program at the epithermal neutron irradiation facility of the Brookhaven Medical Research Reactor. The collimators were constructed from lithium-impregnated polyethylene, which comprises Li2CO3 powder (approximately 93% enriched isotopic 6Li) uniformly dispersed in polyethylene to a total 6Li content of 7.0 wt. %. The first collimator is 7.6 cm thick with a conical cavity 16 cm in diameter on the reactor core side tapering to 8 cm facing the patient's head. The second collimator is 15.2 cm thick with a conical cavity 20 cm in diameter tapering to 12 cm. A clinical trial of BNCT for patients with malignant brain tumors is underway using the first collimator. Results of phantom dosimetry and Monte Carlo computations indicate that the new 15.2 cm thick collimator will improve the neutron beam penetration. Thus, the second collimator was made and will be used in an upcoming clinical trial. In-air and in-phantom mixed-field dosimetric measurements were compared to Monte Carlo computations for both collimators. The deeper penetration is achieved but at a sacrifice in beam intensity. In this report, a performance comparison of both collimators regarding various fluence rate and absorbed dose distributions in a head model is presented and discussed.

Biophysical Phenomena↗
PubMed1994

A comprehensive PC-based computer model for microdosimetry of BNCT.

A computer model is described that performs microdosimetric calculations of the radiation dose delivered to tumour and normal tissue in boron neutron capture therapy (BNCT) by simulating capture reactions in a predefined three-dimensional space. The role of intracellular boron distributions and cellular dimensions on the radiation dose in clinical and experimental BNCT has been studied using a PC-based computer model. In order to calculate the radiation dose to low boron uptake cells, the extent of irradiation by boron containing adjacent cells (cross fire) is also dealt with. Radiation doses from boron and nitrogen neutron capture are converted to a biological effect by means of relative individual ion track segment efficacies, based on linear energy transfer along the particle track. A good correlation was found after comparing predicted values with previously published experimental data. A number of examples is given to illustrate the program's features.

Boron Neutron Capture Therapy↗
PubMed1993

Large animal normal tissue tolerance using an epithermal neutron beam and borocaptate sodium.

Irradiation of the canine head following intravenous Na2B12H11SH (BSH) administration has provided useful information concerning the tolerance of skin and brain to the resultant complex form of irradiation. The effect of the boron capture reaction in skin and brain has provided estimates of the influence of the microscopic dosimetry involved. Dogs irradiated with the epithermal beam alone provided valuable insight into the relative biological effectiveness (RBE) of the fast neutron component (> 10 keV) of the epithermal beam. When compared with literature values for X-rays for the occurrence of skin necrosis in dogs, an RBE of 4.5 was derived. Previous pharmacokinetic data concerning the distribution of Na2B12H11SH (BSH) to blood and brain has been used to obtain input parameters for computer models of the microvasculature of the brain. Monte Carlo computer models were used to simulate the microscopic distribution of BSH in the normal brain. The term compound factor describes the product of the microscopic boron fission fragment dose hitting the nucleus and the relative biologic effectiveness divided by the macroscopic equilibrium dose of the boron reaction in the tissue of interest. The computed compound factor for Na2B12H11SH (BSH) in normal brain was 0.37. This factor agreed very well with the value of 0.32 obtained for the brain necrosis with the dog irradiations. The compound factor for the dog's skin was experimentally derived from the dog experiments and was equal to 0.5.

Animals↗
PubMed1990

Installation and testing of an optimized epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR).

NCT is a binary system, in which 10B is physiologically targeted to tumor and then allowed to interact with thermal neutrons generated in the treatment volume by an externally applied neutron beam. Consequently, an unusually large number of parameters are obtained, which bear on the resultant Therapeutic Gain (TG). However, a perusal of these data, as illustrated in Figure 7, indicates that the TG would increase significantly beyond values projected in this paper if the absolute amount of 10B could be increased above 30 ppm. For example, increasing 10B concentration in tumor to 45 ppm would increase TG by approximately 33% (with a T/N of 5). A similar increase in TG would follow an increase in T/N from 5 to 10. Those associated with the development of boron compounds for NCT feel that such developments are within reach.

Boron Compounds↗
PubMed1990

Neutron spectrum measurements in the aluminum oxide filtered beam facility at the Brookhaven Medical Research Reactor.

Neutron spectrum measurements were performed on the aluminum oxide filter installed in the Brookhaven Medical Research Reactor (BMRR). For these measurements, activation foils were irradiated at the exit port of the beam facility. A technique based on dominant resonances in selected activation reactions was used to measure the epithermal neutron spectrum. The fast and intermediate-energy ranges of the neutron spectrum were measured by threshold reactions and 10B-shielded 235U fission reactions. Neutron spectral data were derived from the activation data by two approaches: (1) a short analysis which yields neutron flux values at the energies of the dominant or primary resonances in the epithermal activation reactions and integral flux data for neutrons above corresponding threshold or pseudo-threshold energies, and (2) the longer analysis which utilized all the activation data in a full-spectrum, unfolding process using the FERRET spectrum adjustment code. This paper gives a brief description of the measurement techniques, analysis methods, and the results obtained.

Aluminum Oxide↗
PubMed1990

Physics design for the Brookhaven Medical Research Reactor epithermal neutron source.

A collaborative effort by researchers at the Idaho National Engineering Laboratory and the Brookhaven National Laboratory has resulted in the design and implementation of an epithermal-neutron source at the Brookhaven Medical Research Reactor (BMRR). Large aluminum containers, filled with aluminum oxide tiles and aluminum spacers, were tailored to pre-existing compartments on the animal side of the reactor facility. A layer of cadmium was used to minimize the thermal-neutron component. Additional bismuth was added to the pre-existing bismuth shield to minimize the gamma component of the beam. Lead was also added to reduce gamma streaming around the bismuth. The physics design methods are outlined in this paper. Information available to date shows close agreement between calculated and measured beam parameters. The neutron spectrum is predominantly in the intermediate energy range (0.5 eV - 10 keV). The peak flux intensity is 6.4E + 12 n/(m2.s.MW) at the center of the beam on the outer surface of the final gamma shield. The corresponding neutron current is 3.8E + 12 n/(m2.s.MW). Presently, the core operates at a maximum of 3 MW. The fast-neutron KERMA is 3.6E-15 cGy/(n/m2) and the gamma KERMA is 5.0E-16 cGY/(n/m2) for the unperturbed beam. The neutron intensity falls off rapidly with distance from the outer shield and the thermal flux realized in phantom or tissue is strongly dependent on the beam-delimiter and target geometry.

Animals↗
PubMedDate not supplied

Demonstration of three-dimensional deterministic radiation transport theory dose distribution analysis for boron neutron capture therapy.

The Monte Carlo stochastic simulation technique has traditionally been the only well-recognized method for computing three-dimensional radiation dose distributions in connection with boron neutron capture therapy (BNCT) research. A deterministic approach to this problem would offer some advantages over the Monte Carlo method. This paper describes an application of a deterministic method to analytically simulate BNCT treatment of a canine head phantom using the epithermal neutron beam at the Brookhaven medical research reactor (BMRR). Calculations were performed with the TORT code from Oak Ridge National Laboratory (ORNL), an implementation of the discrete ordinates, or Sn method. Calculations were from first principles and used no empirical correction factors. The phantom surface was modeled by flat facets of approximately 1 cm2. The phantom interior was homogeneous. Energy-dependent neutron and photon scalar fluxes were calculated on a 32 x 16 x 22 mesh structure with 96 discrete directions in angular phase space. The calculation took 670 min on an Apollo DN10000 workstation. The results were subsequently integrated over energy to obtain full three-dimensional dose distributions. Isodose contours and depth-dose curves were plotted for several separate dose components of interest. Phantom measurements were made by measuring neutron activation (and therefore neutron flux) as a function of depth in copper-gold alloy wires that were inserted through catheters placed in holes drilled in the phantom. Measurements agreed with calculations to within about 15%. The calculations took about an order of magnitude longer than comparable Monte Carlo calculations but provided various conveniences, as well as a useful check.

Animals↗
PubMedDate not supplied

Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy.

Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

Animals↗