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.     

An x-ray CT polymer gel dosimetry prototype: II. Gel characterization and clinical application

This article reports on the dosimetric properties of a new N-isopropylacrylamide, high %T, polymer gel formulation (19.5%T, 23%C), optimized for x-ray computed tomography (CT) polymer gel dosimetry (PGD). In addition, a new gel calibration technique is introduced together with an intensity-modulated radiation therapy (IMRT) treatment validation as an example of a clinical application of the new gel dosimeter. The dosimetric properties investigated include the temporal stability, spatial stability, batch reproducibility and dose rate dependence. The polymerization reaction is found to stabilize after 15 h post-irradiation. Spatial stability investigations reveal a small overshoot in response for gels imaged later than 36 h post-irradiation. Based on these findings, it is recommended that the new gel formulation be imaged between 15-36 h after irradiation. Intra- and inter-batch reproducibility are found to be excellent over the entire range of doses studied (0-28 Gy). A significant dose rate dependence is found for gels irradiated between 100-600 MU?min?1. Overall, the new gel is shown to have promising characteristics for CT PGD, however the implication of the observed dose rate dependence for some clinical applications remains to be determined. The new gel calibration method, based on pixel-by-pixel matching of dose and measured CT numbers, is found to be robust and to agree with the previously used region of interest technique. Pixel-by-pixel calibration is the new recommended standard for CT PGD. The dose resolution for the system was excellent, ranging from 0.2-0.5 Gy for doses between 0-20 Gy and 0.3-0.6 Gy for doses beyond 20 Gy. Comparison of the IMRT irradiation with planned doses yields excellent results: gamma pass rate (3%, 3 mm) of 99.3% at the isocentre slice and 93.4% over the entire treated volume.     

Investigation of the PAGAT polymer gel dosimeter using magnetic resonance imaging

Investigation of the normoxic PAGAT polymer gel dosimeter has been undertaken. The concentrations of the chemical components of the gel were varied and its response to ionizing radiation evaluated. Using MRI, the formulation to give the maximum change in the transverse relaxation rate R2 was determined to be 4.5% N, N'-methylene-bis-acrylamide (bis), 4.5% acrylamide (AA), 5% gelatine, 5 mM tetrakis (hydroxymethyl) phosphonium chloride (THPC), 0.01 mM hydroquinone (HQ) and 86% H2O. The optimal post-manufacture irradiation and post-irradiation imaging times were both determined to be 12 h. The R2-dose response was linear up to 7 Gy with R2-dose sensitivities of (0.183 +/- 0.005) s(-1) Gy(-1), (0.182 +/- 0.005) s(-1) Gy(-1) and (0.192 +/- 0.005) s(-1) Gy(-1) when imaged at 12 h, 7 days and 24 days post-irradiation, respectively. The R2-dose sensitivities were within the range of previously published values for the hypoxic PAG formulations. For the imaging parameters used in this study the optimum dose resolution was achieved for low doses. The normalized R2 edge response showed a high degree of spatial stability over a 24 day period. This study has shown that the normoxic PAGAT polymer gel has the properties of a dosimetric tool, which can be used in clinical radiotherapy. The PAGAT polymer gel has been shown to have similar qualities to the PAG polymer gel, while offering the significant advantage of simplification of the manufacturing procedure.     

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.     

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.     

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.     

Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements

Three-dimensional dosimetry with good spatial resolution can be performed using polymer gel dosimetry, which has been investigated for dosimetry of different types of particles. However, there are only sparse data concerning the influence of the linear energy transfer (LET) properties of the radiation on the gel absorbed dose response. The purpose of this study was to investigate possible LET dependence for a polymer gel dosimeter using proton beam absorbed dose measurements. Polymer gel containing the antioxidant tetrakis(hydroxymethyl)phosphonium (THP) was irradiated with 133 MeV monoenergetic protons, and the gel absorbed dose response was evaluated using MRI. The LET distribution for a monoenergetic proton beam was calculated as a function of depth using the Monte Carlo code PETRA. There was a steep increase in the Monte Carlo calculated LET starting at the depth corresponding to the front edge of the Bragg peak. This increase was closely followed by a decrease in the relative detector sensitivity (Srel = Dgel/Ddiode), indicating that the response of the polymer gel detector was dependent on LET. The relative sensitivity was 0.8 at the Bragg peak, and reached its minimum value at the end of the proton range. No significant effects in the detector response were observed for LET < 4.9 keV microm(-1), thus indicating that the behaviour of the polymer gel dosimeter would not be altered for the range of LET values expected in the case of photons or electrons in a clinical range of energies.     

Optimization of multiple spin-echo sequences for 3D polymer gel dosimetry

The overall performance of polymer gel dosimeters for three-dimensional radiation dosimetry is determined by the temporal and spatial stability of the gels, dose sensitivity and image quality with respect to both systematic and stochastic deviations. The dose resolution (D(p)delta) is determined by the dose sensitivity and the signal-to-noise ratio (SNR) in the dose images. The dose sensitivity can be altered by changing the chemical composition of the polymer gel. The SNR is determined by the scanner and the imaging sequence. In the dose verification of conformal radiotherapy treatments the chosen number of slices may reach a number of 10-20. For these experiments, to obtain a sufficient SNR within a reasonable measurement time using a certain MR scanner, the imaging sequence should be optimized. A few other studies have emphasized the importance of optimizing the imaging sequence with respect to dose resolution (D(p)delta) or SNR but do not give quantitative values for the optimal sequence parameters for scanning a polymer gel dosimeter in three dimensions. In this paper, it is proved that a multiple spin-echo sequence is preferable to a single spin-echo sequence. It is also shown that when using a multiple spin-echo sequence it is not the inter-echo time that should be optimized but the number of echoes. An algebraical expression is derived for the dose resolution in terms of sequence parameters. A mathematical formalism and look-up tables are provided that can be used to optimize both a single and a slice-selective multiple spin-echo sequence to acquire a set of dose images at various locations. The use of the optimization protocol is illustrated by some examples. The optimization protocol enables the user to derive the optimal sequence parameters to acquire a set of dose maps obtained by quantitative T2 imaging for each polymer gel dosimeter within the shortest time possible.     

The relationship between radiation-induced chemical processes and transverse relaxation times in polymer gel dosimeters

The effects of ionizing radiation in different compositions of polymer gel dosimeters are investigated using FT-Raman spectroscopy and NMR T2 relaxation times. The dosimeters are manufactured from different concentrations of comonomers (acrylamide and N,N'-methylene-bis-acrylamide) dispersed in different concentrations of an aqueous gelatin matrix. Results are analysed using a model of fast exchange of magnetization between three proton pools. The fraction of protons in each pool is determined using the known chemical composition of the dosimeter and FT-Raman spectroscopy. Based on these results, the physical and chemical processes in interplay in the dosimeters are examined in view of their effect on the changes in T2. The precipitation of growing macroradicals and the scavenging of free radicals by gelatin are used to explain the rate of polymerization. The model describes the changes in T2 as a function of the absorbed dose up to 50 Gy for the different compositions. This is expected to aid the theoretical design of new, more efficient dosimeters, since it was demonstrated that the optimum dosimeter (i.e, with the lowest dose resolution) must have a range of relaxation times which match the range of T2 values which can be determined with the lowest uncertainty using an MRI scanner.     

An investigation of the chemical stability of a monomer/polymer gel dosimeter

The aim of this work is to investigate the temporal stability of a polyacrylamide gelatin hydrogel used for 3D monomer/polymer gel dosimetry techniques involving different methods of analysis. Long-term instabilities for a similar gel have recently been reported, but differ markedly from those described in this work. Two kinds of long-term instabilities are described. One affects the slope of the dose-R2 plot and is related to post-irradiation polymerization of the comonomer/polymer aggregates. It is observed that post-irradiation polymerization only lasts 12 hours after irradiation. The other instability affects the intercept of the dose-R2 plot, lasts for up to 30 days and is related to the gelation process of gelatin. Further studies were performed on gelatin gels of varying compositions to obtain a better understanding of the molecular mechanism that causes the instability due to gelation. The studies included observations of the spin-spin and spin-lattice relaxation rates in combination with diffusion measurements and optical measurements. It is shown that the heating history during the manufacture of the gel affects the absolute R2 value of the gel but not its variation. The findings presented in this study may help in producing more stable and reproducible monomer/polymer gel dosimeters.     

A preliminary study of the novel application of normoxic polymer gel dosimeters for the measurement of CTDI on diagnostic x-ray CT scanners

Computer tomography dose index (CTDI) is a measurement undertaken during acceptance testing and subsequent quality assurance measurements of diagnostic x-ray CT scanners for the determination of patient dose. Normoxic polymer gel dosimeters have been used for the first time to measure dose and subsequently CTDI during acceptance testing of a CT scanner and compared with the conventional ionization chamber measurement for a range of imaging protocols. The normoxic polymer gel dosimeter was additionally used to simultaneously determine slice-width dose profiles and CTDI in the transaxial plane, the measurements of which are usually determined with thermoluminescent dosimetry or film. The resulting CTDI for all slice widths calculated from the normoxic polymer gel dosimeter were within corresponding ionization chamber CTDI values. Slice-width dose-profiles full-width half-maximum values from the normoxic polymer gel dosimeter were compared to the slice sensitivity profiles and were within the tolerances of the manufacturer. Normoxic polymer gel dosimeters have been shown to be a useful device for determining CTDI and dose distributions for CT equipment, and provide additional information not possible with just the use of an ionization chamber.     

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.     

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.     

Modelling the dynamic dose response of an nMAG polymer gel dosimeter

Gel dosimetry measures the absorbed radiation dose with high spatial resolution in 3D. However, recently published data show that the response of metacrylic-based polymer gels depends on the segmented delivery pattern, which could potentially be a considerable disadvantage for measurements of modern dynamic radiotherapy techniques. The aim of this study is to design a dynamic compartment model for the response of a gel dosimeter, exposed to an arbitrary irradiation pattern (segmented delivery and intensity modulation), in order to evaluate the associated effects on absorbed dose measurements. The model is based on the separation of the protons affecting the magnetic resonance signal (i.e. the R2 value) into six compartments, described by a set of differential equations. The model is used to calculate R2 values for a number of different segmented delivery patterns between 0-4 Gy over 1-33 fractions. Very good agreement is found between calculated and measured R2 values, with an average difference of 0.3 ± 1.1% (1 SD). The model is also used to predict the behaviour of a gel dosimeter exposed to irradiation according to typical IMRT, VMAT and respiratory gating scenarios. The calculated R2 values are approximately independent of the segmented delivery, given that the same total dose is delivered during the same total time. It is concluded that this study helps to improve the theoretical understanding of the dependence of metacrylic-based polymer gel response to segmented radiation delivery.     

An evaluation of the dosimetric performance characteristics of N-vinylpyrrolidone-based polymer gels

The aim of this work was to investigate the dosimetric performance properties of the N-vinylpyrrolidone argon (VIPAR) based polymer gel as a dosimetric tool in clinical radiotherapy. VIPAR gels with a larger concentration of gelatin than the standard recipe were manufactured and irradiated up to 68 Gy using a 6 and 18 MV linear accelerator. Using MRI, the R2-dose response was recorded at different imaging sessions within a 34 day time period post-irradiation. The R2-dose response was found to be linear between 5 and 68 Gy. Although dose sensitivity did not show significant variation with time, the measured R2-dose values showed an increasing trend, which was less evident beyond 17 days. At one day post-irradiation, calculated dose standard uncertainties at 20 Gy and 56 Gy were 2.2% and 1.7%, providing a dose resolution of 0.45 Gy and 0.97 Gy, respectively. Although these values fulfilled the 2% limit of ICRU, when gels were imaged at one day post-irradiation, it was shown that the temporal evolution of the R2 values deteriorated the per cent standard uncertainty and the dose resolution by approximately 57%, when imaged 17 days post-irradiation. Variation in the coagulation temperature of the gels did not impact the R2-dose sensitivity. This study has shown that the VIPAR gel has the properties of a dosimetric tool required in clinical radiotherapy, especially in applications where a wide dose dynamic range is employed. For results with the lowest per cent uncertainty and the optimum dose resolution, the dosimetry gels used in this work should be MR scanned at one day post-irradiation. Furthermore, a preliminary study on the R2-dose response of a new normoxic N-vinylpyrrolidone-based polymer gel showed that it could potentially replace the traditional VIPAR gel formulation, while preserving the wide dynamic dose response inherent to that monomer.     

Attenuation of diagnostic energy photons by polymer gel dosimeters

Post-irradiation changes in the linear attenuation coefficient, mu, of polymer gel dosimeters give rise to a change which can be measured with x-ray computed tomography. Polymer gel dosimeters were manufactured consisting of 3% (by weight) acrylamide and 3% N,N'-methylene-bis-acrylamide comonomers dissolved in aqueous gelatin (5% gelatin by total weight and 89% de-ionized distilled water). Mu was measured in a collimated radiation beam of photons from an 241Am source. Density, rho, of polymer gel dosimeters was measured using volumetric flasks with capillary stoppers. The measured post-irradiation data of mu was plotted against the data of rho for different batches, and linear least squares fits gave r2 values of 0.99605 and 0.99953, with P values of less than 0.001. This confirms that the post-irradiation change in mu is proportional to that of rho. The change in rho implies a change in volume regardless of the evaluation modality of the polymer gel dosimeter.     

新型辐射剂量测量计:聚合体凝胶剂量计

新的更为复杂的放射治疗技术要求辐射剂量计能够准确的测量三维剂量分布,提供高的空间分辨率.聚合体凝胶剂量计是最近才发展的新型剂量计,能够很好的解决三维剂量分布测量的问题.现综述聚合体凝胶剂量计的原理、制备、特性、成像、刻度方法和医学应用.     

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.     

Experimental 3D dosimetry around a high-dose-rate clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter.

It is well known that the experimental dosimetry of brachytherapy sources presents a challenge. Depending on the particular-dosimeter used, measurements can suffer from poor spatial resolution (ion chambers), lack of 3D information (film) or errors due to the presence of the dosimeter itself distorting the radiation flux. To avoid these problems, we have investigated the dosimetry of a clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter. Experimental measurements of dose versus radial distance from the centre of the source (cross-line plots) were compared with calculations produced with a Nucletron NPS planning system. Good agreement was found between the planning system and gel measurements in planes selected for analysis. Gel dosimeter measurements in a coronal plane through the phantom showed a mean difference between measured absorbed dose and calculated dose of 0.17 Gy with SD = 0.13 Gy. Spatially, the errors at the reference point remain within one image pixel (1.0 mm). The use of polymer gel dosimetry shows promise for brachytherapy applications, offering complete, three-dimensional dose information, good spatial resolution and small measurement errors. Measurements close to the source, however, are difficult, due to some of the limiting properties of the polyacrylamide gel.