Investigating potential physicochemical errors in polymer gel dosimeters

Measurement errors in polymer gel dosimetry can originate either during irradiation or scanning. One concern related to the exothermic nature of polymerization reaction was that the heat released in polymer gel dosimeters during irradiation modifies their dose response. In this paper, the effect of heat released from the exothermal polymerization reaction on the dose response of a number of dosimeters was studied. In addition, we investigated whether heat-generated geometric distortion existed in newly proposed gel dosimeters that contain highly thermoresponsive polymers. Our results suggest that despite a significant internal temperature increase in some gel compositions, their dose responses are not affected when oxygen is well expelled mechanically from the gel mixture. We also report on significant pre-irradiation instability in some recently developed polymer gel dosimeters but that geometric distortions were not observed. Data obtained by a set of small calibration vials are compared to those obtained from larger phantoms, and potential physicochemical causes of deviations between them are identified.     

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.     

The fundamental radiation properties of normoxic polymer gel dosimeters: a comparison between a methacrylic acid based gel and acrylamide based gels

Polymer gel dosimeters offer a wide range of applications in the three-dimensional verification of complex dose distributions such as in intensity-modulated radiotherapy. One of the major difficulties with polymer gel dosimeters is their sensitivity to oxygen, as oxygen inhibits the radiation-induced polymerization reaction. For several years, oxygen was removed from the gels by bubbling the sol with inert gases for several hours during the gel fabrication. Also, the gel had to be poured in containers with low oxygen permeability and solubility. Recently, it was found that these technical difficulties can easily be solved by adding an antioxidant to the gel. These gels are called 'normoxic' gels as they can be produced under normal atmospheric conditions. In this study several properties of polymer gel dosimeters have been investigated: the dose sensitivity, the temporal and spatial stability of the gel, the sensitivity of the dose response to temperature during irradiation and during MR imaging, the energy dependence and the dose-rate dependence. This study reveals that the normoxic polymer gel dosimeter based on methacrylic acid (nMAG) studied in this work has inferior radiation properties as compared to the polyacrylamide gelatine (PAG) gel dosimeters. It is shown that from the three different gel dosimeters investigated in this study, the nPAG gel dosimeter results in a less sensitive gel dosimeter but with superior radiation properties as compared to the nMAG gel dosimeter. The importance of investigating relevant radiation properties of gel dosimeters apart from the radiation sensitivity-prior to their use for dosimetric validation experiments-is illustrated and emphasized throughout this study. Other combinations of monomer and gelling agent may result in more reliable normoxic polymer gel dosimeters.     

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.     

Effects of glass and backscatter on measurement of absorbed dose in polyacrylamide gel (PAG) dosimeters

Different methodologies are used for calibrating polyacrylamide gel (PAG) dosimeters. One methodology involves injecting nitrogen-filled glass vials with polymer gel. Due to the vials being pre-filled with nitrogen, a nitrogen-filled space remains in the glass vial above the gel. The glass vial is then irradiated using ionizing radiation to polymerize the PAG. Monte Carlo simulations were performed to examine the effects on the radiation field due to the glass vial and the lack of backscatter material due to the nitrogen-filled space. Results for two different formulations of PAG indicated that the influence of the glass and the nitrogen-filled space are negligible.     

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.     

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.     

Study of the relative dose-response of BANG-3 polymer gel dosimeters in epithermal neutron irradiation

Polymer gels have been reported as a new, potential tool for dosimetry in mixed neutron-gamma radiation fields. In this work, BANG-3 (MGS Research Inc.) gel vials from three production batches were irradiated with 6 MV photons of a Varian Clinac 2100 C linear accelerator and with the epithermal neutron beam of the Finnish boron neutron capture therapy (BNCT) facility at the FiR 1 nuclear reactor. The gel is tissue equivalent in main elemental composition and density and its T2 relaxation time is dependent on the absorbed dose. The T2 relaxation time map of the irradiated gel vials was measured with a 1.5 T magnetic resonance (MR) scanner using spin echo sequence. The absorbed doses of neutron irradiation were calculated using DORT computer code, and the accuracy of the calculational model was verified by measuring gamma ray dose rate with thermoluminescent dosimeters and 55Mn(n,gamma) activation reaction rate with activation detectors. The response of the BANG-3 gel dosimeter for total absorbed dose in the neutron irradiation was linear, and the magnitude of the response relative to the response in the photon irradiation was observed to vary between different gel batches. The results support the potential of polymer gels in BNCT dosimetry, especially for the verification of two- or three-dimensional dose distributions.     

Investigation of ultrasonic properties of PAG and MAGIC polymer gel dosimeters

Ultrasonic speed of propagation and attenuation were investigated as a function of absorbed radiation dose in PAG and MAGIC polymer gel dosimeters. Both PAG and MAGIC gel dosimeters displayed a dependence of ultrasonic parameters on absorbed dose with attenuation displaying significant changes in the dose range investigated. The ultrasonic attenuation dose sensitivity at 4 MHz in MAGIC gels was determined to be 4.7 +/- 0.3 dB m(-1) Gy(-1) and for PAG 3.9 +/- 0.3 dB m(-1) Gy(-1). Ultrasonic speed dose sensitivities were 0.178 +/- 0.006 m s(-1) Gy(-1) for MAGIC gel and -0.44 +/- 0.02 m s(-1) Gy(-1) for PAG. Density and compressional elastic modulus were investigated to explain the different sensitivities of ultrasonic speed to radiation for PAG and MAGIC gels. The different sensitivities were found to be due to differences in the compressional elastic modulus as a function of dose for the two formulations. To understand the physical phenomena underlying the increase in ultrasonic attenuation with dose, the viscoelastic properties of the gels were studied. Results suggest that at ultrasonic frequencies, attenuation in polymer gel dosimeters is primarily due to volume viscosity. It is concluded that ultrasonic attenuation significantly increases with absorbed dose. Also, the ultrasonic speed in polymer gel dosimeters is affected by changes in dosimeter elastic modulus that are likely to be a result of polymerization. It is suggested that ultrasound is a sufficiently sensitive technique for polymer gel dosimetry.     

Polymer gel dosimetry using x-ray computed tomography: a feasibility study

A new three-dimensional dosimetry technique using x-ray computed tomography (CT) to analyse polymer gels is proposed. The CT imaging is sensitive to radiation-induced density changes that occur within irradiated polyacrylamide gel (PAG). In this preliminary study, a CT imaging protocol is developed to optimize CT images of PAG; the response of PAG CT number to dose (N(CT)-dose response) and the reproducibility of the response are investigated, and the use of CT to analyse PAG is compared with MRI. Experiments were conducted using two 1.5 l cylindrical PAG phantoms (3% acrylamide, 3% bis and 5% gelatin by weight), one irradiated with four intersecting 10 MV photon beams and the other with 10 sets of 6 MV parallel opposed circular radiosurgery fields. The final imaging protocol involves using optimum CT parameters (120 kVp and 200 mAs for our GE HiSpeed CT/i scanner), image averaging and background subtraction. The N(CT)-dose response is reproducible, linear up to 800-1000 cGy and is relatively insensitive to the gel temperature during imaging. The dose resolution is approximately 50 cGy for an image thickness of 10 mm. Despite the low dose resolution, preliminary results indicate that this CT technique provides accurate localization of high dose gradients such as those observed in stereotactic radiosurgery. Thus, given the availability and speed of CT scanners, the technique has the potential to be a valuable and practical 3D dose verification tool in radiation therapy.     

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.     

Severe dose inaccuracies caused by an oxygen-antioxidant imbalance in normoxic polymer gel dosimeters

Two oxygen scavengers have been successfully tested to produce normoxic polymer gel dosimeters under normal atmospheric conditions. The first is ascorbic acid and the second is a chloride (also sulfate) salt of tetrakis (hydroxymethyl) phosphonium. These antioxidants, added to the dosimeter during gel preparation, chemically remove dissolved oxygen that otherwise inhibits propagation of the polymerization reaction during irradiation of the dosimeter. These gel dosimeters are radiosensitive after manufacture under normoxic conditions. However, we show herein that the accuracy of the dosimetric measurement is compromised due to chemical reactions of the antioxidant with radicals. In addition, we provide evidence that both antioxidant and oxygen act as radical scavengers that affect the amount of polymer formed in the gel dosimeter. This can result in important dose inaccuracies in both methacrylic acid-based and acrylamide-based normoxic dosimeter gels.     

The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R(2) was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5-35 s(-1) with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally irradiated gels. Curve fits to the calibration data followed a single exponential function. The correlation coefficients for internally and externally irradiated gels were 0.991 and 0.985, respectively. With the ability to accurately calibrate internally dosed polymer gels, this technology shows promise as a means to evaluate dosimetry methods, particularly in cases of non-uniform uptake of a radionuclide.     

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.     

Wistar大鼠的咬肌放射损伤模型

背景：构建稳定可靠的咬肌放射损伤模型对颌面部肿瘤放疗的相关研究有重要意义。 目的：以放射剂量40 Gy照射后Wistar大鼠咬肌构建大鼠咬肌放射损伤模型。 方法：成年Wistar大鼠20只,随机分成正常对照组和放射损伤组。放射损伤组采用直线加速器照射大鼠咬肌区累积40 Gy制造咬肌放射损伤。在28 d后,在光镜及电镜下观察咬肌放射区病理改变,RT-PCR检测转化生长因子β1的基因表达。 结果与结论：40 Gy照射后28 d大鼠咬肌区出现结构受损、血管密度减低(P < 0.01)等放射损伤表现,同时引起转化生长因子β1的基因表达升高(P < 0.001)等机体被动修复表现。结果证实Wistar大鼠咬肌区直线加速器40 Gy照射可以作为咬肌放射损伤模型。     

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.     

Measurement of ultrasonic attenuation coefficient in polymer gel dosimeters

A technique is described for investigation of the ultrasonic attenuation coefficient for evaluation of absorbed dose in polymer gel dosimeters. Using this technique the attenuation coefficient as a function of absorbed dose in PAG and MAGIC polymer gel dosimeters was measured. The ultrasonic attenuation coefficient dose sensitivity for PAG was found to be 2.9 +/- 0.3 dB m(-1) Gy(-1) and for MAGIC gel 4.2 +/- 0.3 dB m(-1) Gy(-1). Unlike previous studies of ultrasonic attenuation in polymer gel dosimeters this technique enables a direct measure of the attenuation coefficient.     

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.     

Change of properties during storage of a UDMA/TEGDMA dental resin

The aim of this study was to evaluate the changes in viscoelastic properties of a UDMA-based dental resin as a function of time after initial light exposure. Specimens of a UDMA/TEGDMA (70:30 wt%) resin were irradiated by a visible-light-curing unit. Immediately after the irradiation, the light-cured specimen was stored in the dark for different times from 1 to 120 h at 37 degrees C, and characterized by means of DMA, DSC, and FTIR spectroscopy. The irradiated specimen exhibited a bimodal shape in the form of two rapid declines in log E' corresponding to glass transition with a plateau between the two declines. Two distinct peaks were seen in tan delta versus temperature. The thermal reaction of the incompletely cured sample with residual groups trapped by the fast reaction during irradiation is responsible for the plateau. After storage, significant changes were observed in dynamic mechanical parameters, DSC exotherm, and degree of conversion. Storage modulus continued to increase during the 4 h of storage and leveled off thereafter. Peak heights of tan delta versus temperature were also influenced by storage. Degree of conversion increased from 75 +/- 2% immediately after irradiation to 87 +/- 3% after 120 h storage. The changes of the properties of this dental resin system when stored at 37 degrees C after irradiation are clinically important in terms of stability, durability, and performance after initial polymerization.     

Photopolymerization of dental composite matrices

The kinetic behaviour of dental composite is traditionally studied, considering only the isothermal behaviour, whereas a fast and highly non-isothermal bulk polymerization is expected as a consequence of the significant heat developed due to the exothermic nature of the polymerization reaction. In this paper the photopolymerization kinetics of a commercial dental composite activated by visible light are analysed by differential scanning calorimetry. This technique is applied to determine the degree of reaction and the glass transition temperature of thin layers of the composite matrix, at different isothermal cure temperatures. A phenomenological kinetic model is then integrated with an energy balance in order to analyse the cure behaviour of thicker composite layers. The full model results indicate that non-isothermal cure conditions may be achieved, obtaining higher values for the glass transition temperature and the degree of reaction. Biomaterials (1994) 15, 1221–1228