Biomedical subjects

W V Prestwich

Publications and source records attributed to W V Prestwich.

At least 19 recordsLinked to original sources

PubMed2005

Monte Carlo simulation of neutron irradiation facility developed for accelerator based in vivo neutron activation measurements in human hand bones.

The neutron irradiation facility developed at the McMaster University 3 MV Van de Graaff accelerator was employed to assess in vivo elemental content of aluminum and manganese in human hands. These measurements were carried out to monitor the long-term exposure of these potentially toxic trace elements through hand bone levels. The dose equivalent delivered to a patient during irradiation procedure is the limiting factor for IVNAA measurements. This article describes a method to estimate the average radiation dose equivalent delivered to the patient's hand during irradiation. The computational method described in this work augments the dose measurements carried out earlier [Arnold et al., 2002. Med. Phys. 29(11), 2718-2724]. This method employs the Monte Carlo simulation of hand irradiation facility using MCNP4B. Based on the estimated dose equivalents received by the patient hand, the proposed irradiation procedure for the IVNAA measurement of manganese in human hands [Arnold et al., 2002. Med. Phys. 29(11), 2718-2724] with normal (1 ppm) and elevated manganese content can be carried out with a reasonably low dose of 31 mSv to the hand. Sixty-three percent of the total dose equivalent is delivered by non-useful fast group (> 10 keV); the filtration of this neutron group from the beam will further decrease the dose equivalent to the patient's hand.

Aluminum↗

PubMed2005

In vivo measurement of bone aluminium: recent developments.

A biomarker of aluminium accumulation in the human body can play a valuable role in determining health effects of chronic aluminium exposure, complementing other human and environmental monitoring data. In vivo neutron activation provides such a non-invasive biomarker. To date, the best in vivo neutron activation system used thermalised neutrons from a nuclear reactor at Brookhaven National Laboratory, which suffered only slightly from interference from other elements, primarily phosphorus, and from the disadvantage of restricted accessibility. At McMaster, we use a nuclear reaction on an accelerator to select neutron energy, which eliminates the interferences. Spectral decomposition analysis improved sensitivity. A new 4pi detection system also enhanced sensitivity. Together these improvements yield a minimum detection limit of 0.24 mgAl in a hand, slightly better than at Brookhaven and equivalent to "normal" levels. Further improvements should result from a new irradiation cavity and from using a higher proton current on the accelerator to shorten irradiation times. The system is now ready for pilot human studies.

Aluminum↗

PubMed2004

Application of spectral decomposition analysis to in vivo quantification of aluminum by neutron activation analysis.

The toxic effects of aluminum are cumulative and result in painful forms of renal osteodystrophy, most notably adynamic bone disease and osteomalacia, but also other forms of disease. The Trace Element Group at McMaster University has developed an accelerator-based in vivo procedure for detecting aluminum body burden by neutron activation analysis (NAA). Further refining of the method was necessary for increasing its sensitivity. In this context, the present study proposes an improved algorithm for data analysis, based on spectral decomposition. A new minimum detectable limit (MDL) of (0.7+/-0.1)mg Al was reached for a local dose of (20+/-1)mSv. The study also addresses the feasibility of a new data acquisition technique, the electronic rejection of the coincident events detected by a NaI(Tl) system. It is expected that the application of this technique, together with spectral decomposition analysis, would provide an acceptable MDL for the method to be valuable in a clinical setting.

Algorithms↗

PubMed2003

Lithium target performance evaluation for low-energy accelerator-based in vivo measurements using gamma spectroscopy.

The operating conditions at McMaster KN Van de Graaf accelerator have been optimized to produce neutrons via the (7)Li(p, n)(7)Be reaction for in vivo neutron activation analysis. In a number of earlier studies (development of an accelerator based system for in vivo neutron activation analysis measurements of manganese in humans, Ph.D. Thesis, McMaster University, Hamilton, ON, Canada; Appl. Radiat. Isot. 53 (2000) 657; in vivo measurement of some trace elements in human Bone, Ph.D. Thesis. McMaster University, Hamilton, ON, Canada), a significant discrepancy between the experimental and the calculated neutron doses has been pointed out. The hypotheses formulated in the above references to explain the deviation of the experimental results from analytical calculations, have been tested experimentally. The performance of the lithium target for neutron production has been evaluated by measuring the (7)Be activity produced as a result of (p, n) interaction with (7)Li. In contradiction to the formulated hypotheses, lithium target performance was found to be mainly affected by inefficient target cooling and the presence of oxides layer on target surface. An appropriate choice of these parameters resulted in neutron yields same as predicated by analytical calculations.

Humans↗

PubMed2003

Development of a low-energy monoenergetic neutron source for applications in low-dose radiobiological and radiochemical research.

The McMaster University 3 MV KN Van de Graff accelerator facility primarily dedicated to in vivo neutron activation measurements has been used to produce moderate dose rates of monoenergetic fast neutrons of energy ranging from 150 to 600 keV with a small energy spread of about 25 keV (1sigma width of Gaussian) by bombarding thin lithium targets with 2.00-2.40 MeV protons. The calculated dose rate of the monoenergetic neutrons produced using thin lithium targets as functions of beam energy, target thickness, lab angle relative to beam direction, and the solid angle subtended by the sample with the target has also been reported.

Equipment Design↗

PubMed2003

Investigating the TEPC radiation quality factor response for low energy accelerator based clinical applications.

The use of a tissue equivalent proportional counter (TEPC) filled with propane based tissue equivalent gas simulating a 2 microm diameter tissue sphere has been investigated to estimate the radiation quality factor of the neutron fields used in in vivo neutron activation measurements at the McMaster University 3 MV Van de Graaff accelerator. The counter response to estimate the effective quality factor based on the definitions of Q(L) provided in ICRP 26 and 60 as a function of neutron energy has been examined experimentally using monoenergetic and continuous neutron spectra in the energy range of 35 to 600 keV. In agreement with other studies, the counter failed to provide a flat R(Q) response and showed a sharp drop below 200 keV neutron energy. Development of an algorithm to evaluate the quality factors using measured dose-mean lineal energy, yD, and comparison of the algorithm with other reported algorithms and analytical methods developed for the improvement in TEPC dose equivalent response has been reported.

Algorithms↗

PubMed2001

Calculation of radiation-induced DNA damage from photons and tritium beta-particles. Part I: Model formulation and basic results.

Radiation-induced damage in nucleosomal DNA was modelled by Monte Carlo means. An atomistic representation of DNA with a first hydration shell was used. DNA single- and double-strand break (SSB and DSB) yields were calculated for 137Cs photons, x-rays and tritium beta-particles. Monte Carlo-generated electron tracks for liquid water were used to model energy deposition. Chemical evolution of a track and interactions between species and DNA following water radiolysis were modelled in an encounter-controlled manner. The effects of varying the scavenging capacity of the environment, the extent of DNA protection by histones and the setting of a threshold for direct energy depositions on DNA break yields were all systematically studied. DSB complexity was assessed in terms of DNA breaks and base damage accompanying a DSB. Model parameters were adjusted to make predictions consistent with experimental data on DSB yields and yield modification by a variety of factors including changing DNA conformation and incorporation of scavengers. An embedded model of nucleosomal DNA by histones was required to explain experimentally observed modification of DSB yield by removal of bound histones. Complex DSB, defined as DSB accompanied by an additional strand breakage, exhibited high association with base damage. It is shown that hydroxyl radical interactions with bases are a major contributor to DSB complexity. On average there were 1.15 and 2.69 OH-base interactions accompanying simple and complex DSB, respectively for 137Cs. Over 80% of complex DSB had at least one OH-base interaction associated with a DNA break.

Beta Particles↗

PubMed2001

Calculation of radiation-induced DNA damage from photons and tritium beta-particles. Part II: Tritium RBE and damage complexity.

Yields of DNA single- and double-strand breaks (SSB and DSB) in nucleosomal DNA were calculated for 137Cs, 70 keV photons and tritium beta-particles by Monte Carlo means. Monte Carlo-generated electron tracks for liquid water were used to model energy deposition. Chemical evolution of a track and interactions between species and DNA following water radiolysis were modelled in an encounter-controlled manner. The calculated relative biological effectiveness (RBE) for DSB production for tritium against 137Cs was 1.2 for the total DSB yield. Tritium beta-particles were slightly more efficient compared to 137Cs in producing complex DSB, defined as DSB accompanied by additional strand breaks. The RBE for complex DSB formation was 1.3. Most complex DSB exhibited associated base damage; the extent of the base damage was similar for all the radiation types considered. Correlated DSB conforming to nucleosome periodicity were observed. However, their frequency was low, of the order of 2% of total DSB. For all the DNA damage endpoints considered and their response to variation of the scavenging environment or DNA conformation no difference was observed between 70 keV photons and tritium beta-particles.

Beta Particles↗

PubMed2000

Dose measurement based on spectral chi-square minimization using GAFchromic MD-55 film.

A new method of measuring dose using GAFchromic MD-55-2 type film is proposed. It involves 2D fitting of optical density, as a function of both wavelength and dose, to a set of measured calibration data. An unknown dose to a film can then be determined by minimizing the chi-square between the measured optical densities and the fitted calibration data. The methodology was tested, using 60Co calibration, by measuring the dose deposited in films irradiated by a 32p source in a semi-infinite geometry. The results are compared with the expected dose obtained From beta counting, taking into account the dose loss correction due to various attenuating materials, including the film substrate itself, which was determined to be 20%. It was found that the root mean relative deviation between the measured and expected doses was approximately 3%. The excellent agreement also demonstrated the possibility of calibration between gamma and beta particles.

Beta Particles↗

PubMed2000

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Animals↗

PubMed1998

The cellular environment in computer simulations of radiation-induced damage to DNA.

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in a cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x10(9) dm3 mol(-1) s(-1). Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10(-9) s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage.

Cells↗

PubMed1998

Modelling DNA damage induced by different energy photons and tritium beta-particles.

PURPOSE: To model the production of single- and double-strand breaks (ssb and dsb) in DNA by ionizing radiations. To compare the predicted effectiveness of different energy photon radiations and tritium beta-particles. MATERIALS AND METHODS: Modelling is carried out by Monte Carlo and includes consideration of direct energy depositions in DNA molecules, the production of species, their diffusion and interactions with each other and DNA. Computer-generated electron tracks in liquid water are used to model energy deposition and to derive the initial positions of chemical species. Atomistic representation of the DNA in B form with a first hydration shell is used. Photon radiations in the energy range 70keV-1MeV and tritium beta-particles are considered. RESULTS: A tentative increase for dsb yield has been predicted for 70 keV photons and tritium compared with 137Cs. This increase is more pronounced for complex dsb. Double-strand breaks are much more prone compared with ssb to combine with additional strand breaks and base damage, which contributes to break complexity. At least half of DNA breaks are hydroxyl radical mediated. CONCLUSIONS: The developed model makes predictions compatible with features of available experimental data. Break complexity has to be addressed in biophysical modelling when the relative effectiveness of radiations in DNA damage is studied. Obtained data strongly argue against the dominance of direct radiation action in DNA damage in the cellular environment predicted by some theoretical studies.

Computer Simulation↗

PubMed1998

Monte Carlo simulation of source-excited in vivo x-ray fluorescence measurements of heavy metals.

This paper reports on the Monte Carlo simulation of in vivo x-ray fluorescence (XRF) measurements. Our model is an improvement on previously reported simulations in that it relies on a theoretical basis for modelling Compton momentum broadening as well as detector efficiency. Furthermore, this model is an accurate simulation of experimentally detected spectra when comparisons are made in absolute counts; preceding models have generally only achieved agreement with spectra normalized to unit area. Our code is sufficiently flexible to be applied to the investigation of numerous source-excited in vivo XRF systems. Thus far the simulation has been applied to the modelling of two different systems. The first application was the investigation of various aspects of a new in vivo XRF system, the measurement of uranium in bone with 57Co in a backscatter (approximately 180 degrees) geometry. The Monte Carlo simulation was critical in assessing the potential of applying XRF to the measurement of uranium in bone. Currently the Monte Carlo code is being used to evaluate a potential means of simplifying an established in vivo XRF system, the measurement of lead in bone with 57Co in a 90 degrees geometry. The results from these simulations may demonstrate that calibration procedures can be significantly simplified and subject dose may be reduced. As well as providing an excellent tool for optimizing designs of new systems and improving existing techniques, this model can be used in the investigation of the dosimetry of various XRF systems. Our simulation allows a detailed understanding of the numerous processes involved when heavy metal concentrations are measured in vivo with XRF.

Biophysical Phenomena↗

PubMed1998

A statistical investigation of the scaling factor method of beta-ray dose distribution derivation: the scaling factor for water to bone.

Reliable methods of estimating doses are essential for the use of beta emitting radionuclides for radiotherapy. The passage of electrons through matter is a very complex phenomenon due to the large number of elastic and inelastic interactions resulting in scattering and energy losses. The analytical solution for the electron transport being intractable, the problem has been addressed by the Monte Carlo technique. Empirical or semiempirical less time consuming methods, such as the scaling factor method, may appear more preferable in practice when dealing with complicated source distributions. The method, proposed by Cross and co-workers [AECL Report Nos. AECL-1617 (1982), AECL 10521 (1992)] consists in the derivation of beta-ray dose distribution in other media from those in water by using a "scaling factor" or "relative attenuation factor" on distance and a closely related renormalization factor imposed by the energy conservation. This work investigates the accuracy of the scaling factor method using a statistical approach, a generalized chi 2 test, focusing on the particular case of potential interest, the scaling factor for water to bone. The direct comparison of the shapes of the depth dose deposition curves in the two media indicates discrepancies of less than 5% up to at least 60% of the range in bone, a depth within which 95% of the initial energy is deposited. The scaling factor derived by this method, 0.9720 +/- 0.0012, confirms the existing experimentally determined value of 0.973 +/- 1% [AECL Report No. AECL-10521 (1992)]. The accuracy of the determination is increased by almost a factor of 10. A way of improving the scaling method, especially for depth over the 60% continuous slowing down approximation range, by using a modulation function is also proposed.

Beta Particles↗

PubMed1998

Application of the scaling factor method to estimation of beta dose distributions for dissimilar media separated by a planar interface.

The most accurate method of calculating beta dose distribution currently relies on the Monte Carlo technique. The major drawback of the method is the long computing time required to follow a large number of "electron histories" in order to achieve good statistics, which makes the method unattractive for practical radiation therapy. A way to avoid the Monte Carlo calculations for homogeneous media was suggested by Cross and co-workers (AECL Report Nos. 7617, 1982; 10521, 1992), and is known as the "scaling factor" method. It consists of the determination of the depth dose distribution in a medium based on known data about the dose distribution in an arbitrary reference medium (e.g., air, water) by the use of a scaling factor on distance and a closely related renormalization factor imposed by energy conservation. This work is an attempt to extend the applicability of the scaling factor method to dissimilar media to a planar interface. The investigation was done for an isotropic source of the radioisotope 32P and an interface between water and medium "i," where medium "i" could be any medium with atomic number in the range 8 < Z < 50. The method was checked using three randomly chosen elements 40Zr, 32Ge, and 26Fe, each forming planar interfaces with water at either 100 or 350 mg/cm2. Discrepancies of less than 5% were detected (acceptable for practical radiotherapy) for the depth within which at least 95% of the initial energy is deposited.

Beta Particles↗

PubMed1997

Energy deposition pattern from tritium and different energy photons--a comparative study.

Energy deposition patterns of beta particles from tritium decay have been analyzed in comparison with photon radiation in the energy range from 12 to 1250 keV. Energy deposition was modeled by Monte Carlo means using electron tracks in water vapor with a complete follow up of delta electrons. Ionizations have been used as representative of track structure. Frequencies of clusters on a nanometer scale and their spatial distribution in spherical targets representing cell nuclei have been derived. Cluster analysis has been carried out by implementing a k-means method. Frequencies of ionization clusters from tritium are similar to 60-100 keV photons. Spatial distribution of clusters from tritium closely match approximately 70 keV photons up to 2 microm separation.

Monte Carlo Method↗

PubMed1997

The influence of track structure on the understanding of relative biological effectiveness for induction of chromosomal exchanges in human lymphocytes.

A biophysical model has been applied to describe the production of exchange chromosomal aberrations (dicentrics) in human lymphocytes by radiations of different qualities. The model includes a detailed description of the energy deposition pattern in the form of computer-generated tracks. Energy deposition events are further converted to DNA double-strand breaks (DSBs). Formation of chromosomal exchanges is modeled in competition with repair in a distance-dependent manner with breaks in proximity being most likely to interact. We demonstrate that an assumption of an RBE > 1 for production of DSBs at higher LET leads to a significant increase with LET of both the linear and the quadratic coefficients of the dose response for exchange formation. The latter is not supported experimentally and argues against high RBE values for production of DSBs, at least for those breaks involved in chromosomal exchanges. Assuming that the RBE for production of DSBs is unity, the calculated dose-response curves conformed to experimental data for 60Co gamma rays, 250 kVp X rays and 8.7 MeV protons. The linear coefficient for 23.5 MeV 3He ions is underpredicted. The model predicts that a quadratic term in the dose response for exchange aberrations should be observed at LET values of 20-30 keV/microm. The curvature is not observed experimentally, and the contradiction is discussed.

Alpha Particles↗

PubMed1996

Analytic representation of the dose from a 32P-coated stent.

The dose along the radial direction located at the midplane of a radioactive stent, simulated by a uniform cylinder of 32P, is represented by an analytical function consisting of the sum of two modified exponentials. This procedure reproduces values obtained from numerical integration, for which no closed form exists, to within 5% for distances up to 6 mm from the wall and for stent diameters from 2-6 mm.

Angioplasty↗