Modelling of post-irradiation events in polymer gel dosimeters.

The nuclear magnetic resonance (NMR) spin-spin relaxation time (T2) is related to the radiation-dependent concentration of polymer formed in polymer gel dosimeters manufactured from monomers in an aqueous gelatin matrix. Changes in T2 with time post-irradiation have been reported in the literature but their nature is not fully understood. We investigated those changes with time after irradiation using FT-Raman spectroscopy and the precise determination of T2 at high magnetic field in a polymer gel dosimeter. A model of fast exchange of magnetization taking into account ongoing gelation and strengthening of the gelatin matrix as well as the polymerization of the monomers with time is presented. Published data on the changes of T2 in gelatin gels as a function of post-manufacture time are used and fitted closely by the model presented. The same set of parameters characterizing the variations of T2 in gelatin gels and the increasing concentration of polymer determined from FT-Raman spectroscopy are used successfully in the modelling of irradiated polymer gel dosimeters. Minimal variations in T2 in an irradiated PAG dosimeter are observed after 13 h.     

Development and optimization of a 2-hydroxyethylacrylate MRI polymer gel dosimeter

In this study, radiation induced changes in a polymer gel dosimeter manufactured using 2-hydroxyethylacrylate (HEA) and N,N'-methylene-bisacrylamide (BIS) were investigated using magnetic resonance imaging (MRI) and FT-Raman spectroscopy. The variation in magnetic resonance relaxation time (T2) with absorbed dose was modelled assuming fast exchange of magnetization. Overall good agreement between the model and experimental data was obtained. However, comparison with FT-Raman data suggests that not all the protons attached to the polymer contribute to the relaxation process. Furthermore, for certain compositions improved agreement with experimental data was achieved when a lower fraction of polymer protons available for exchange with water was assumed in the low dose region. This indicates that the T2 value is influenced by the composition and topology of the formed polymer, which may vary with absorbed dose. The concept of percentage dose resolution (Dp delta, %) was introduced to enable optimization of gel compositions for use in relative dosimetry applications. This concept was applied to demonstrate the effects of varying the gelatine concentration, the total fraction of monomer/crosslinker (%T) and the relative fraction of crosslinker (%C) on gel performance in HEA gels as well as compare the performance of HEA and a standard polyacrylamide gel (PAG). The percentage dose resolution was improved for all HEA gels compared to the PAG dosimeter containing 3% acrylamide and 3% BIS. Increasing the total concentration of monomer was shown to have the largest single effect. In the range of doses of interest for clinical radiation therapy, Dp delta, % for the optimal HEA gel (4% HEA, 4% BIS) was lower than 2.3%, compared to 3.8% for the PAG dosimeter.     

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.     

An experimental study of the dose response of polymer gel dosimeters imaged with x-ray computed tomography.

Changes in the linear attenuation coefficient of polymer gel dosimeters post-irradiation enable the imaging of dose distributions by x-ray computed tomography (CT). Various compositions of polymer gel dosimeters manufactured from acrylamide (AA), and N,N'-methylene-bis-acrylamide (BIS) comonomers and gelatin or agarose gelling agents were investigated. This work shows that increasing the comonomer concentration increases the CT-dose sensitivity of the polymer gel dosimeter. This can be further increased by replacing gelatin with agarose. Varying the gelatin concentration however does not significantly change the CT-dose sensitivity. Among the compositions studied, dose resolution (D(delta)95%) was found to be optimal for polymer gel dosimeters comprising 5% gelatin, 3% AA, 3% BIS and 89% water.     

Dose-response characteristics of a ferrous-sulphate-doped gelatin system for determining radiation absorbed dose distributions by magnetic resonance imaging (Fe MRI)

The nuclear magnetic resonance (NMR) longitudinal relaxation rate R1 dose-response characteristics of a ferrous-sulphate-doped chemical dosimeter system (Fe MRI) immobilized in a gelatin matrix were explored. Samples containing various concentrations of the FeSO4 dosimeter were irradiated to absorbed doses of 0-150 Gy. R1 relaxation rates were determined by imaging the samples at a field strength of 1.5T(1H Lamor frequency of 63.8 MHz). The response of the system was found to be approximately linear up to doses of 50 Gy for all FeSO4 concentrations studied (0.1-2.0 mM). Changing concentrations in the range of 0.1-0.5 mM affected both the slope and intercept of the dose-response curve. For concentrations of 0.5-2.0 mM, the slope of the dose-response curves remained constant at approximately 0.0423 s-1 Gy-1 in the dose range of 0-50 Gy. However, the intercept of the curve continued to increase in that region, as expected, because of the additional paramagnetic ions. The reproducibility of the absorbed dose estimates for measurements made over a 22 cm field of view was found to be 5% in the range of 20-50 Gy (an uncertainty of 0.81 Gy on average), decreasing to approximately 10% in the dose range of 5-10 Gy.     

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose-response using different monomers

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.     

Dose-response stability and integrity of the dose distribution of various polymer gel dosimeters

In this study the stability of different polymer gel dosimeters is investigated. Further to a previous chemical stability study on a (6%T, 50%C) PAG gel, the change in slope and intercept of the linear part of the R2-dose plot is recorded with time for different gel formulations. In addition to this R2-dose-response stability study, the dose edge of a half-blocked field was recorded with time. Three different PAG type polymer gels, a hydroxyethyl acrylate (HEA) gel and two different normoxic polymer gels were investigated. In the PAG type polymer gels, the relative concentration of gelatin and comonomers was varied in order to study the influence of the different components, that constitute the dosimeter, on the stability. It is shown that the R2-dose-response stability is largely determined by the chemical composition of the gel dosimeters. All the PAG gel dosimeters and the normoxic gel dosimeters are found to preserve the integrity of the dose distribution up to 22 days after irradiation. The half-life of the change in dose sensitivity of a MAGIC gel is found to be 18 h compared to 5.7 h for a (6%T, 50%C) PAG gel. A maximum relative decrease in dose sensitivity of 21% was noted for the MAGIC gel compared to an increase of 50% for a (6%T, 50%C) PAG gel. A loss of integrity of the dose distribution was found in the HEA gel.     

Preliminary studies on the role and reactions of tetrakis(hydroxymethyl)phosphonium chloride in polyacrylamide gel dosimeters

A major source of dosimetric inaccuracy in normoxic polymer gel dosimeters is local variations in the concentration of oxygen scavenger. Currently, a phosphorus compound, tetrakis(hydroxymethyl)phosphonium chloride (THPC), is the oxygen scavenger of choice in most polymer gel dosimetry studies. Reactions of THPC in a gel dosimeter are not limited to oxygen. It can possibly be consumed in reacting with gelling agent, water free-radicals and polymer radicals before, during and after irradiation, hence affecting the dose response of the dosimeter in several ways. These reactions are not fully known or understood. It is our hypothesis that THPC not only scavenges radical species but also modifies the morphology of the gelatin network and of the polymer, possibly by intervening in the polymerization of monomers. These hypotheses are investigated in an anoxic acrylamide-based gel dosimeter. Scanning electron microscopy results indicate gelatin pores decreasing from 70 to 40?μm and a very different radiation-induced polymer structure in samples containing THPC; Fourier-transform Raman spectroscopy shows a two-fold reduction in the dose constants of monomer consumption; however, a significant change in the relative dose constants of monomer consumption as a function of dose could not be detected.     

Radio-physical properties of micelle leucodye 3D integrating gel dosimeters

Recently, novel radiochromic leucodye micelle hydrogel dosimeters were introduced in the literature. In these studies, gel measured electron depth dose profiles were compared with ion chamber depth dose data, from which it was concluded that leucocrystal violet-type dosimeters were independent of dose rate. Similar conclusions were drawn for leucomalachite green-type dosimeters, only after pre-irradiating the samples to a homogeneous radiation dose. However, in our extensive study of the radio-physical properties of leucocrystal violet- and leucomalachite green-type dosimeters, a significant dose rate dependence was found. For a dose rate variation between 50 and 400 cGy min(-1), a maximum difference of 75% was found in optical dose sensitivity for the leucomalachite green-type dosimeter. Furthermore, the measured optical dose sensitivity of the leucomalachite green-type dosimeter was four times lower than the value previously reported in the literature. For the leucocrystal violet-type dosimeter, a maximum difference in optical dose sensitivity of 55% was found between 50 and 400 cGy min(-1). A modified composition of the leucomalachite green-type dosimeter is proposed. This dosimeter is composed of gelatin, sodium dodecyl sulfate, chloroform, trichloroacetic acid and leucomalachite green. The optical dose sensitivity amounted to 4.375 × 10(-5) cm(-1) cGy(-1) (dose rate 400 cGy min(-1)). No energy dependence for photon energies between 6 and 18 MV was found. No temperature dependence during readout was found notwithstanding a temperature dependence during irradiation of 1.90 cGy °C(-1) increase on a total dose of 100 cGy. The novel gel dosimeter formulation exhibits an improved spatial stability (2.45 × 10(-7) cm(2) s(-1) (= 0.088 mm(2) h(-1))) and good water/soft tissue equivalence. Nevertheless, the novel formulation was also found to have a significant, albeit reduced, dose rate dependence, as a maximum difference of 33% was found in optical dose sensitivity when the dose rate varied between 50 and 400 cGy min(-1). By pre-irradiating the novel leucomalachite green-type dosimeter to 500 cGy, the apparent difference in dose response between 200 and 400 cGy min(-1) was eliminated, similar to earlier findings. However, a dose response difference of 38% between 50 and 200 cGy min(-1) was still measured. On the basis of these experimental results it is concluded that the leucodye micelle gel dosimeter is not yet optimal for dose verifications of high precision radiation therapy treatments. This study, however, indicates that the dose rate dependence has a potential for improvement. Future research is necessary to further minimize the dose rate dependence through extensive chemical analysis and optimization of the gel formulation. Some insights into the physicochemical mechanisms were obtained and are discussed in this paper.     

The influence of cooling rate on the accuracy of normoxic polymer gel dosimeters

Polymer gel dosimeters offer a wide range of applications in the three-dimensional verification of complex radiation dose distributions such as in intensity-modulated radiotherapy (IMRT). With the release of polymer gel dosimeters that can be fabricated in normal atmospheric ('normoxic') conditions, the gel manufacturing process has been significantly simplified. Gel dosimeters are calibrated by use of a series of calibration vials irradiated with known doses or by use of a calibration phantom with a known dose distribution. The overall accuracy of the polymer gel dosimeters is determined by different dosimetric properties. In this study, we show the influence of the temperature history during storage of the gel dosimeter on the dose response curve for two gel dosimeters using the monomers acrylamide/N,N'-methylene-bis-acrylamide (nPAG) and methacrylic acid (nMAG) respectively and bis[tetrakis(hydroxymethyl)phosphonium]sulphate (THP) as antioxidant in both gel dosimeters. This study reveals that differences in temperature history after fabrication of normoxic polymer gel dosimeters may compromise the dosimetric accuracy. It was found that the acrylamide based gel dosimeter (nPAG) is less dependent on the post-manufacture temperature history than the methacrylic acid based gel dosimeter (nMAG). The importance of an equal temperature history for the gel dosimeter and calibration vials is emphasized by this study. A reproducibility study has also been performed on the nPAG gel dosimeter when additional efforts are made to control the temperature changes upon cooling.     

Dose resolution optimization of polymer gel dosimeters using different monomers.

Polymer gel dosimeters of different formulations were manufactured from different monomers of acrylamide, acrylic acid, methacrylic acid, 1-vinyl-2-pyrrolidinone, 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate. Gelatin and agarose were used as the gelling agents and N,N'-methylene-bis-acrylamide was used as a co-monomer in each polymer gel dosimeter. The T2 dependence of each dosimeter was analysed using a model of fast exchange of magnetization. The influence of the half-dose and the apparent T2 of the polymer-proton pool on the dose resolution (Dpdelta) were examined. Comparisons are made with the commonly employed R2-dose sensitivity. Differences exist suggesting that experiments reported in the literature using what were thought to be more optimal dosimeters may not actually be so. Based on Dpdelta of each formulation, conclusions are drawn on the optimal formulation required for a specific range of absorbed doses. In addition, information about the extent of polymerization of the monomers used along with some characteristics of the polymer network formed are reported. The influence of the concentration of monomers and gelling agent was subsequently evaluated using a model of fast exchange of magnetization. Based on these calculations, further improvement in Dpdelta can be expected.     

Detection of radiation effects in polymer gel dosimeters using 129Xe NMR

Polymer gel dosimeters consist of monomers, with or without cross-linking agents, dispersed in a gel. Upon exposure to ionizing radiation, polymerization proceeds within the gel matrix, thereby changing several measurable physical properties that can then be related quantitatively to absorbed dose. Several previous studies have examined how various nuclear magnetic resonance (NMR) properties, such as the relaxation rates of water protons, change with dose, and magnetic resonance imaging (MRI) has been used successfully to measure three-dimensional dose distributions in irradiated polymer gels. Here we report our first observations of the manner in which the chemical shift of xenon gas (129Xe) dissolved in a gel changes with absorbed dose, and we introduce the potential use of high resolution xenon NMR spectra for understanding better the dose response of gels. 129Xe possesses a large chemical shift range and xenon spectra are sensitive to subtle changes in the physical and chemical environments in which the gas is dissolved. For doses ranging from 0 Gy to 40 Gy we found that the mean chemical shift of 129Xe was linearly related to dose, and that the gel dosimeter could be described in terms of a two-component model undergoing fast exchange. We found no evidence of radiation damage to the gelatin matrix at doses between 0 Gy and 40 Gy. At 40 Gy, the fast-exchange model begins to break down, and distinct gelatin and poly(methacrylate) resonances are observed at higher doses. High resolution NMR measurements of xenon provide a novel method for probing radiation dose effects in irradiated polymer gels.     

On the relation between the spatial dose integrity and the temporal instability of polymer gel dosimeters

When irradiating a polymer gel dosimeter to relatively high doses, edge enhancing effects (overshoots) may be noticed near dose gradients, resulting in a loss of spatial dose integrity. These overshoots are believed to be a consequence of monomers diffusing into the high-dose region, where they react with long-living macroradicals. Macroradicals may also be responsible for the temporal chemical instability of post-irradiation polymerization that occurs in the polymer gel dosimeter. In this study, a mathematical model is proposed that simulates the edge enhancing effect. The model is based on the hypothesis that the macroradicals are responsible for both the temporal instability and loss of spatial dose integrity. All input parameters for the model are obtained from independent experiments. The edge enhancing effect is studied both experimentally and theoretically for polymer gel dosimeters with various gelatin concentrations. The change in the edge enhancement is also investigated over post-irradiation time. Comparisons between polymer gel measurements and simulations confirm the hypothesis that there is a strong relation between the spatial and temporal instabilities.     

Magnetic resonance imaging of radiation dose distributions using a polymer-gel dosimeter

A new formulation of a tissue-equivalent polymer-gel dosimeter for the measurement of three-dimensional dose distributions of ionizing radiation has been developed. It is composed of aqueous gelatin infused with acrylamide and N, N'-methylene-bisacrylamide monomers, and made hypoxic by nitrogen saturation. Irradiation of the gel, referred to as BANG, causes localized polymerization of the monomers, which, in turn, reduces the transverse NMR relaxation times of water protons. The dose dependence of the NMR transverse relaxation rate, R2, is reproducible (less than 2% variation) and is linear up to about 8 Gy, with a slope of 0.25 s(-1)Gy(-1) at 1.5 T. Magnetic resonance imaging may be used to obtain accurate three-dimensional dose distributions with high spatial resolution. Since the radiation-induced polymers do not diffuse through the gelatin matrix, the dose distributions recorded by BANG gels are stable for long periods of time, and may be used to measure low-activity radioactive sources. Since the light-scattering properties of the polymerized regions are different from those of the clear, non-irradiated regions, the dose distributions are visible, and their optical densities are dependent on dose.     

Uncertainty analysis in polymer gel dosimetry

Verification of advanced radiotherapy treatment modalities requires measurement of three-dimensional absorbed dose distributions with high spatial resolution and precision. Polymer gel dosimeters combined with magnetic resonance imaging may be able to fulfil this requirement. However, verification requires that the uncertainty in the dosimeter is well known. One method of estimating the overall uncertainty in polymer gel dosimeters involves the propagation of the uncertainty in the R2 (nuclear magnetic resonance relaxation rate) map and the uncertainties in the calibration data. This work shows that using this method with current data suggests that the lowest uncertainty currently obtainable is about 3% at 8 Gy and 7% at 2 Gy. Furthermore, the most significant reductions in overall uncertainty will be achieved by reducing the noise in the R2 map.     

Dose resolution in radiotherapy polymer gel dosimetry: effect of echo spacing in MRI pulse sequence

In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in absorbed dose is dependent on the experimental determination of T2. The concept of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied to the uncertainty in dose related to the uncertainty in T2 from a range of T4 encountered in polymer gel dosimetry. Dpdelta is defined as the minimal separation between two absorbed doses such that they may be distinguished with a given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the dose approaches zero. Dpdelta and the minimum detectable dose both give a quantifiable indication of the likely practical limitations and usefulness of the dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner. In evaluating uncertainties in T2, a parameter of particular significance in the pulse sequence is the echo spacing (ES). For optimal results, ES should be selected to minimize Dpdelta over a range of doses of interest in polymer gel dosimetry.     

Effects of crosslinker fraction in polymer gel dosimeters using FT Raman spectroscopy

Radiation-induced chemical changes in polyacrylamide gels (PAGs) used in 3D radiation dosimetry have been studied using Fourier transform Raman spectroscopy. Consumption of monomer and crosslinker were characterized for polymer gel dosimeters with initial fraction of crosslinker (%C) varying from to 100%. Results indicate that the rate of monomer/crosslinker consumption is highly nonlinear over %C. This indicates that maximum polymer gel dosimeter sensitivity (i.e. slope of the monomer consumption curves) is dependent not only on initial %C but also on dose range. For low-dose regions (<5 Gy) 30%C PAGs are the most sensitive dosimeters, their maximum sensitivity being a factor of 1.8 times greater than 50%C PAGs. In mid-dose range (S-15 Gy), however, 50%C PAGs are the most sensitive dosimeters, being potentially a factor of 1.3 more sensitive than any other PAG studied. In high-dose regions (> 15 Gy) 70%C PAGs are at least 1.5 times more sensitive than any other PAG studied. A qualitative model is presented which helps to explain the variation in overall monomer consumption rate as a function of initial %C. The variation in the shapes (i.e. mathematical course) of the consumption curves for different %C PAGs is, in part, qualitatively explained by consideration of the average number of monomer to crosslinker molecules available for reaction in each PAG as it is irradiated to higher doses. Finally, we demonstrate the importance of an existing polymer network on the subsequent monomer consumption rate in a 50%C PAG.     

A spin-spin relaxation rate investigation of the gelatin ferrous sulphate NMR dosimeter

Spin-spin NMR relaxation rate in the ferrous sulphate gelatin dosimeter has been studied in terms of pH, gelatin concentration, the addition of benzoic acid, and sample size. It is demonstrated that R2 is more sensitive to changes in Fe3+ ion concentration than R1 when measuring at frequencies of 64 and 100 MHz. pH has an important effect on dose response curves, and oxygen depletion occurs significantly more rapidly in FeSO4 gelatin than in the liquid FeSO4, resulting in a saturation dose of approximately 80 Gy at depths greater than approximately 3 mm in phantom. The concentration of gelatin can be increased to 12% by weight, and the dosimeter will continue to exhibit a linear dose response. Sensitivity is maintained at higher gel concentrations by pH compensation. Addition of low-concentration benzoic acid to the system does not alter the dose response of the gelatin FeSO4 system. Finally, spontaneous oxidation of Fe2+ ions does not significantly alter the shape of dose response curves but does result in increases in R2 by up to 4% per day.     

Investigation of tetrakis hydroxymethyl phosphonium chloride as an antioxidant for use in x-ray computed tomography polyacrylamide gel dosimetry

Of the antioxidants used to scavenge oxygen in polymer gel dosimeters, tetrakis (hydroxymethyl) phosphonium chloride (THPC) has been shown to hold great promise due to its rapid oxygen scavenging abilities. In this study we (a) investigate the use of THPC as an antioxidant for polyacrylamide gel (PAGAT) dosimeters used in conjunction with x-ray computed tomography (CT) and (b) work to establish the reaction mechanisms of THPC with the polymer gel constituents. We establish the dose response reproducibility of PAGAT dosimeters when imaged with CT and show that PAGAT dosimeters exhibit highly reproducible dose responses for a range of irradiation times post gel manufacture (2-6 h) and CT imaging times post gel irradiation (1-5 days). The THPC concentration within the gel leading to a maximized dose response and minimized O(2) inhibition of polymerization is found to be approximately 4.5 mM. We further assess the stability of PAGAT dosimeters by investigating the reactions of THPC with the individual gel constituents. The importance of utilizing deionized water in polymer gel manufacture is noted. We show that, while THPC remains unreactive with acrylamide and bis-acrylamide under unirradiated conditions, THPC can react with gelatin to increase the cross-linking of the gelatin matrix in unirradiated dosimeters. THPC reactions with gelatin can lead to the lower observed dose sensitivity of PAGAT (approximately 0.36 +/- 0.04 H Gy(-1)) as compared to polyacrylamide gels manufactured under anoxic conditions (approximately 0.83 +/- 0.03 H Gy(-1)). The reactions of THPC which lead to O(2) scavenging, and potential reactions of THPC with other gel constituents, are proposed.