Development of an advanced two-dimensional microdosimetric detector based on THick Gas Electron Multipliers.

PURPOSE: The THick Gas Electron Multiplier (THGEM)-based tissue-equivalent proportional counter (TEPC) has been proven to be useful for microdosimetry due to its flexibility in varying the gaseous sensitive volume and achieving high multiplication gain. Aiming at measuring the spatial distribution of radiation dose for mixed neutron-gamma fields, an advanced two-dimensional (2D) THGEM-TEPC was designed and constructed at McMaster University which will enable us to overcome the operational limitation of the classical TEPCs, particularly for high-dose rate fields. Compared to the traditional TEPCs, anode wire electrodes were replaced by a THGEM layer, which not only enhances the gas multiplication gain but also offers a flexible and convenient fabrication for building 2D detectors. METHOD & MATERIALS: The 2D THGEM TEPC consists of an array of 3 × 3 sensitive volumes, equivalent to nine individual TEPCs, each of which has a dimension of 5 mm diameter and length. Taking the overall cost, size and flexibility into account, to process nine detector signals simultaneously, a multi-input digital pulse processing system was developed by using modern microcontrollers, each of which is coupled with a 12-bit sampling ADC. RESULTS: Using the McMaster Tandetron 7 Li(p,n) accelerator neutron source, both fundamental detector performance, as well as neutron dosimetric response of the 2D THGEM-TEPC, has been extensively investigated and compared to the data acquired by a standard spherical TEPC. It was shown that the microdosimetric response and the measured absorbed dose rate of the 2D THGEM detector developed in this study are comparable to the standard 1/2" TEPC which is commercially available. CONCLUSION: This study proved that the 2D TEPC based on the THGEM technology can be effectively used in microdosimetry studies and is a promising detector for measuring the absorbed dose rate distribution over an area in mixed radiation fields. This unique small gas cavity detector opens new possibilities in applications for high-intensity mixed radiation fields as well as in nanodosimetry.

A Pilot Study Measuring Aluminum in Bone in Alzheimer's Disease and control Subjects Using in vivo Neutron Activation Analysis.

Aluminum, being the most abundant metal in the earth's crust, is widely distributed in the environment, and is routinely taken up by the human body through ingestion and inhalation. Aluminum is not considered an essential element and it can be toxic in high concentrations. Most of the body burden of aluminum is stored in the bones. Aluminum has been postulated to be involved in the causality of Alzheimer's disease. A system for non-invasive measurement of bone aluminum using the in vivo neutron activation analysis technique has been developed and previously reported in the literature by our group. The results are reported as ratio of Al to Ca in order to eliminate the variations in beam parameters and geometry as well as the physical variations among the subjects such as size of the hand and bone structure. This pilot study included 30 subjects, 15 diagnosed with Alzheimer's disease in mild and moderate stages and 15 control subjects, all of whom were 60 years of age or older. The mean value of aluminum for the control group was 2.7±8.2µg Al/g Ca (inverse-variance weighted mean 3.5±0.9µg Al/g Ca) and for the Alzheimer's disease subjects was 12.5±13.1µg Al/g Ca (inverse-variance weighted mean 7.6±0.6µg Al/g Ca). The difference between the mean of the Alzheimer's disease group and the mean of the control group was 9.8±15.9µg Al/g Ca, with a p-value of 0.02. An age-dependent linear increase in bone aluminum concentration was observed for all subjects. The difference in serum aluminum levels between the two groups did not reach significance.

Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From (90)Y; Consequences for Radiation Induced Bystander Effects.

In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced "bystander effects" that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to ß-radiation from (90)Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of ß particle irradiation of the Petri-dishes. For a tightly collimated ß-particle beam exposure, we observed 167 photons in the detector per unit µCi in the shielded source for a 1.76 mm thick substrate and 158 photons/µCi for a 0.878 mm thick substrate. A unit µCi source activity was equivalent to an exposure to the substrate of 18 ß-particles/cm(2) in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed that increasing cell density in medium of fixed volume resulted in a decrease in the observed light output. This followed a roughly exponential decline. We suggest that this may be due to increased scattering at the cell boundary and absorption of the UV in the cells. We conclude that we have measured UVA emitted by cells, cell medium and cell substrates as a consequence of their irradiation by low LET ß-particle radiation. We suggest that these secondary UV photons could lead to effects in non-targetted cells. Some effects that had previously been attributed to a chemically mediated "bystander effect" may in fact be due to secondary UV emission. Some radiation bystander effect studies may require re-interpretation as this phenomenon of UV emission is further investigated.

Neutrons do not produce a bystander effect in zebrafish irradiated in vivo.

PURPOSE: Neutron irradiations at the McMaster Tandetron Accelerator were performed to study direct and bystander effects of neutrons in a live organism. METHODS: The neutrons were produced through (7)Li(p,n)(7)Be reaction. Although the gamma contamination of the neutron beam cannot be completely eliminated, it was designed to be as low as possible and remain below a threshold already established for bystander effects. Microdosimetric methods using a tissue-equivalent proportional counter have been used to measure the neutron and gamma doses for the cell irradiation. Previous data for a cell line exposed in vitro suggested that neutrons did not produce bystander effects at doses below 300 mGy. The current experiments sought to confirm this using a live whole organism (zebrafish) where tissue samples harvested 2 h after exposure were examined for direct evidence of apoptosis and tested for secretion of bystander factors using an established bioassay. Fish were either exposed directly to the beam or were allowed to swim with or in water previously occupied by irradiated fish. RESULTS: Using the zebrafish model it was found that there was significant direct cell death seen both by apoptosis scores and clonogenic assay when the neutron dose was approximately 100 mGy. An equivalent dose of gamma rays produced a more toxic effect. It was further found that neutrons did not induce a bystander effect in fish receiving signals from irradiated fish. CONCLUSION: The results confirm in vitro experiments which suggest neutrons do not induce bystander signaling. In fact they may suppress gamma induced signaling suggesting a possible intriguing new and as yet unclear mechanism.

Effective target size for the induction of bystander effects in medium transfer experiments.

Although radiation-induced bystander effects are frequently observed biological phenomena, the mechanism for these effects has not been fully determined. The target-hit theory and related concepts from microdosimetry provide a convenient formalism to help identify the nature of the targets responsible for initiating the emission of diffusible factors in medium transfer experiments. We used the microdosimetric models proposed by Stewart et al. (Radiat. Res. 165, 460-469, 2006) to analyze the results of published medium transfer experiments for gamma-ray doses in the range of 0.04 mGy to 5 Gy. The analysis suggests that the effective size of the target responsible for initiating signal emission in HPV-G human keratinocyte donor cells is approximately 2 microm.

A dose threshold for a medium transfer bystander effect for a human skin cell line.

The existence of radiation-induced bystander effects mediated by diffusible factors is now accepted, but the mechanisms and precise behavior at low doses remain unclear. We exposed cells to gamma-ray doses in the range 0.04 mGy-5 Gy, harvested the culture medium, and transferred it to unirradiated reporter cells. Calcium fluxes and clonogenic survival were measured in the recipients. We show evidence for a dose threshold around 2 mGy for the human skin cell line used with a suggestion of increased survival below that dose. Similar experiments using direct gamma irradiation showed no reduction in survival until the dose exceeded 7 mGy. Preliminary data for neutrons where the gamma-ray dose was kept below the bystander threshold do not show a significant bystander effect in the dose range 1-33 mGy. A lack of a bystander response with neutrons occurred at around 1 Gy, where significant cell killing from direct irradiation was observed. The result may have implications for understanding the role of bystander effects at low doses.

Monte carlo investigation of the dosimetric properties of the new 103Pd BrachySeedPd-103 Model Pd-1 source.

Recently, 103Pd brachytherapy sources have been increasingly used for interstitial implants as an alternative to 125I sources. The BrachySeedPd-103 Model Pd-1 seed is one of the latest in a series of new brachytherapy sources that have become available commercially. The dosimetric properties of the seed were investigated by Monte Carlo simulation, which was performed using the Integrated Tiger Series CYLTRAN code. Following the AAPM Task Group 43 formalism, the dose rate constant, radial dose function, and anisotropy parameters were determined. The dose rate constant, A, was calculated to be 0.613 +/- 3% cGy h(-1) U(-1). This air kerma strength was derived from Monte Carlo simulation using the point extrapolation method. The radial dose function, g(r), was computed at distances from 0.15 to 10 cm. The anisotropy function, F(r,theta), and anisotropy factor, phi(an)(r), were calculated at distances from 0.5 to 7 cm. The anisotropy constant, phi(an), was determined to be 0.978, which is closer to unity than most other 103Pd seeds, indicating a high degree of uniformity in dose distribution. The dose rate constant and the radial dose function were also investigated by analytical modeling, which served as an independent evaluation of the Monte Carlo data, and found to be in good agreement with the Monte Carlo results.

Dosimetric properties of the new 125I BrachySeed model LS-1 source.

The BrachySeed model LS-1 is one of the latest in a series of new brachytherapy 125I seeds that have recently become available commercially for interstitial implants. The dosimetric properties of the seed were investigated analytically, experimentally, and by Monte Carlo simulation. Following the AAPM Task Group 43 formalism, the radial dose function, dose rate constant, and anisotropy parameters were determined. Experimental measurements were made in solid water-equivalent phantoms using GafChromic MD-55-2 films, with correction for the low energy film response. Analyses were carried out from absolute measurements, as well as relative measurements against the Nycomed Amersham OncoSeed Model 6711, which also served to validate our experimental methodology. A small, but systematic difference in the absolute measurements was observed depending on the duration of the irradiation. Monte Carlo simulation was performed using the Integrated Tiger Series CYLTRAN code. We benchmarked the code by comparing the dose parameters of Model 6702 with published values. The radial dose function, g(r), of the Model LS-1 seed was computed at distances from 0.25 to 10 cm by analytical and Monte Carlo calculations with reasonably good agreement. The suggested dose rate constant, A, based on the Monte Carlo simulation is 0.90+/-0.03 cGy h(-1) U(-1). This value is smaller than, but overlaps the experimental determination of 0.98+/-0.06 cGy h(-1) U(-1). The anisotropy function, F(r, theta), and anisotropy factor, phi(an)(r), compared favorably with those of the Model 6711.