Imaging of radiation dose by visible color development in ferrous-agarose-xylenol orange gels

Imaging of radiation dose distribution in gel phantoms by magnetic resonance techniques has previously been reported. In this paper a method of producing gels in which the distributions of radiation dose can also be visualized as a color change is reported. The color developed depends qualitatively and quantitatively on the concentrations of solutes in the gel.     

Ultrasound evaluation of polymer gel dosimeters

A new method for the evaluation of radiotherapy 3D polymer gel dosimeters has been developed using ultrasound to assess the significant structural changes that occur following irradiation of the dosimeters. The ultrasonic parameters of acoustic speed of propagation, attenuation and transmitted signal intensity were measured as a function of absorbed radiation dose. The dose sensitivities for each parameter were determined as 1.8 x 10(-4) s m(-1) Gy(-1), 3.9 dB m(-1) Gy(-1) and 3.2 V(-1) Gy(-1) respectively. All parameters displayed a strong variation with absorbed dose that continued beyond absorbed doses of 15 Gy. The ultrasonic measurements demonstrated a significantly larger dynamic range in dose response curves than that achieved with previously published magnetic resonance imaging (MRI) dose response data. It is concluded that ultrasound shows great potential as a technique for the evaluation of polymer gel dosimeters.     

Radiological properties of normoxic polymer gel dosimeters

The radiological properties of the normoxic polymer gel dosimeters MAGIC, MAGAS, and MAGAT [methacrylic and ascorbic acid in gelatin initiated by copper; methacrylic acid gelatine gel with ascorbic acid; and methacrylic acid gelatine and tetrakis (hydroxymethyl) phosphonium chloride, respectively] have been investigated. The radiological water equivalence was determined by comparing the polymer gel macroscopic photon and electron interaction cross sections over the energy range from 10 keV to 20 MeV and by Monte Carlo modeling of depth doses. Normoxic polymer gel dosimeters have a high gelatine and monomer concentration and therefore mass density (kg m(-3)) up to 3.8% higher than water. This results in differences between the cross-section ratios of the normoxic polymer gels and water of up to 3% for the attenuation, energy absorption, and collision stopping power coefficient ratios through the Compton dominant energy range. The mass cross-section ratios were within 2% of water except for the mass attenuation and energy absorption coefficients ratios, which showed differences with water of up to 6% for energies less than 100 keV. Monte Carlo modeling was undertaken for the polymer gel dosimeters to model the electron and photon transport resulting from a 6 MV photon beam. The absolute percentage differences between gel and water were within 1% and the relative percentage differences were within 3.5%. The results show that the MAGAT gel formulation is the most radiological water equivalent of the normoxic polymer gel dosimeters investigated due to its lower mass density measurement compared with MAGAS and MAGIC gels.     

Determining optimal gel sensitivity in optical CT scanning of gel dosimeters

A method for determining the gel sensitivity that is necessary for obtaining optimal image contrast in optical CT scanning of gel dosimeters is presented. The effective dynamic range of the OCTOPUS-ONE research scanner (MGS Research, Inc., Madison, CT) is analyzed. Optical density increments for selected straight-line paths across a gel cylinder to be scanned are calculated based on the optical properties of the polymer gel and the dose distribution from a commercial treatment planning system (Cadplan, Varian Corporation, Palo Alto, CA). Maximum optical density increment across the entire gel is obtained by searching the gel cylinder over a set of transverse planes at different rotational angles. The application of this quantity as a criterion for optimizing the quality of the optical CT scanning is demonstrated through dose verification of two representative treatment plans. When the MU dependence of the dose distribution for a treatment plan is linear, as is the case for static field irradiation, it is possible to scale the treatment plan such that the intensity variation of the signals received by the photodetector spans its entire dynamic range. For treatment plans that are possibly nonlinear, IMRT plans, for example, modification of the sensitivity of the gel material is necessary for the high-dose signals to be collected at a certain signal-to-noise ratio. Results obtained using the optimized CT scanning approach are compared with those from the treatment planning system and the film measurement.     

Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response

This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range (~0.88 H Gy(-1)) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent (~0.80 H Gy(-1)). This new gel formulation results in enhanced dose resolution (~0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.     

A basic study of some normoxic polymer gel dosimeters

Polymer gel dosimeters offer a wide range of potential applications in the three-dimensional verification of complex dose distribution such as in intensity-modulated radiotherapy (IMRT). Until now, however, polymer gel dosimeters have not been widely used in the clinic. One of the reasons is that they are difficult to manufacture. As the polymerization in polymer gels is inhibited by oxygen, all free oxygen has to be removed from the gels. For several years this was achieved by bubbling nitrogen through the gel solutions and by filling the phantoms in a glove box that is perfused with nitrogen. Recently another gel formulation was proposed in which oxygen is bound in a metallo-organic complex thus removing the problem of oxygen inhibition. The proposed gel consists of methacrylic acid, gelatin, ascorbic acid, hydroquinone and copper(II)sulphate and is given the acronym MAGIC gel dosimeter. These gels are fabricated under normal atmospheric conditions and are therefore called 'normoxic' gel dosimeters. In this study, a chemical analysis on the MAGIC gel was performed. The composition of the gel was varied and its radiation response was evaluated. The role of different chemicals and the reaction kinetics are discussed. It was found that ascorbic acid alone was able to bind the oxygen and can thus be used as an anti-oxidant in a polymer gel dosimeter. It was also found that the anti-oxidants N-acetyl-cysteine and tetrakis(hydroxymethyl)phosphonium were effective in scavenging the oxygen. However, the rate of oxygen scavenging is dependent on the anti-oxidant and its concentration with tetrakis(hydroxymethyl)phosphonium being the most reactive anti-oxidants. Potentiometric oxygen measurements in solution provide an easy way to get a first impression on the rate of oxygen scavenging. It is shown that cupper(II)sulphate operates as a catalyst in the oxidation of ascorbic acid. We, therefore, propose some new normoxic gel formulations that have a less complicated chemical formulation than the MAGIC gel.     

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.     

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.     

CCD imaging for optical tomography of gel radiation dosimeters

Several investigations have been carried out by a number of researchers over the past few years to evaluate the utility of imaging gel dosimeters for the three-dimensional measurement of radiation fields. These have been proposed to be of particular value in mapping radiation dose distributions associated with emerging and complex approaches to cancer treatment such as conformal (CRT), intensity modulated (IMRT), "gamma knife," and pencil beam radiotherapies. Imaging of the gels has been successfully accomplished with clinical MRI units and via laser-based optical scanning. However, neither of these methods is generally accessible to all potential users, limiting the broader study and implementation of this valuable tool. We report here the design, methodology, and results of a preliminary study carried out to evaluate the utility of a new, inexpensive, and simplified approach to tomographic imaging of gel radiation dosimeters. For the purpose of this initial investigation, an array of liquid scintillation vials was prepared, containing a ferrous sulphate xylenol orange (FSX) gelatin formulation. The FSX formulation undergoes a change in optical absorption characteristics following irradiation, and the resulting color change can be observed visually. The vials were irradiated individually to different doses. Three-dimensional imaging was accomplished by tomographic reconstruction from two-dimensional optical images acquired using a diffuse, fluorescent light source, a digital charge-coupled device camera, single-photon-emission-computed tomography software, and other simple components designed by the authors. The resulting transverse images were evaluated through a region-of-interest (ROI) analysis to obtain the average change in image density in each vial as a function of radiation dose. These measured ROI values were subjected to a linear regression analysis to fit them to a straight line, and to determine the goodness of fit. Results from multiple imaging trials are compared. The correlation coefficients obtained are typically on the order of 0.98, and the p value from analysis of variance is approximately 0.05, indicating a linear and reproducible response for the dosimeter formulation and imaging system.     

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.     

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.     

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.     

Experimental study of attenuation properties of normoxic polymer gel dosimeters

The change in linear attenuation coefficient with absorbed dose has been investigated for aqueous polyacrylamide, gelatine and tetrakis (PAGAT) and aqueous methacrylic acid, gelatine and tetrakis (MAGAT) normoxic polymer gel dosimeters using tetrakis (hydroxy methyl) phosphonium chloride as the antioxidant. The measured linear attenuation coefficient increased linearly with absorbed dose up to 15 Gy for PAGAT gels and 10 Gy for MAGAT gels. Computerized tomography (CT) numbers or Hounsfield units (H) were calculated from the linear attenuation coefficients and compared with values obtained using a CT scanner. Both calculated and measured CT numbers followed a similar pattern when fitted with a biexponential curve. The CT numbers obtained from linear attenuation measurements were found to be greater than that obtained with the CT scanner for both PAGAT and MAGAT polymer gels. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters measured on a CT scanner were calculated to be (0.85 +/- 0.08) H Gy(-1) and (0.31 +/- 0.03) H Gy(-1), respectively. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters from attenuation measurements were found to be (1.10 +/- 0.66) H Gy(-1) and (0.34 +/- 0.01) H Gy(-1), respectively.     

An apparent threshold dose response in ferrous xylenol-orange gel dosimeters when scanned with a yellow light source

Freshly prepared radiochromic ferrous xylenol-orange (FX) gels optically scanned with a light source exhibit a threshold dose response that is thermally and wavelength dependent. Correction for this threshold dose leads to accurate dose calibration and better reproducibility in multiple fraction radiation exposures. The objective of this study was to determine the cause of the threshold dose effect and to control it through improved dose calibration procedures. The results of a systematic investigation into the chemical cause revealed that impurities within the various FX gel constituents (i.e. xylenol-orange, gelatin, sulfuric acid and ferrous ammonium sulfate) were not directly responsible for the threshold dose. Rather, it was determined that the threshold dose response stems from a spectral sensitivity to different chemical complexes that are formed at different dose levels in FX gels between ferric (Fe(III)) ions and xylenol-orange (XO), i.e. Fe(III)i:XOj. A double Fe(III)2:XO1 complex preferentially absorbs at longer wavelengths (i.e. yellow), while at shorter wavelengths (i.e. green) the sensitivity is biased toward the single Fe(III)1:XO1 complex. As a result, when scanning with yellow light, freshly prepared FX gels require a minimum concentration of Fe(III) ions to shift the equilibrium concentration to favor the predominant production of the double Fe(III)2:XO1 complex at low doses. This can be accomplished via pre-irradiation of freshly prepared gels to a priming dose of approximately 0.5 Gy or allowing auto-oxidation to generate the startup concentration of Fe(III) ions required to negate the apparent threshold dose response.     

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.     

Proton spectroscopic imaging of polyacrylamide gel dosimeters for absolute radiation dosimetry

Proton spectroscopy has been evaluated as a method for quantifying radiation induced changes in polyacrylamide gel dosimeters. A calibration was first performed using BANG-type gel samples receiving uniform doses of 6 MV photons from 0 to 9 Gy in 1 Gy intervals. The peak integral of the acrylic protons belonging to acrylamide and methylenebisacrylamide normalized to the water signal was plotted against absorbed dose. Response was approximately linear within the range 0-7 Gy. A large gel phantom irradiated with three, coplanar 3 x 3 cm square fields to 5.74 Gy at isocentre was then imaged with an echo filter technique to map the distribution of monomers directly. The image, normalized to the water signal, was converted into an absolute dose map. At the isocentre the measured dose was 5.69 Gy (SD = 0.09) which was in good agreement with the planned dose. The measured dose distribution elsewhere in the sample shows greater errors. A T2 derived dose map demonstrated a better relative distribution but gave an overestimate of the dose at isocentre of 18%. The data indicate that MR measurements of monomer concentration can complement T2-based measurements and can be used to verify absolute dose. Compared with the more usual T2 measurements for assessing gel polymerization, monomer concentration analysis is less sensitive to parameters such as gel pH and temperature, which can cause ambiguous relaxation time measurements and erroneous absolute dose calculations.     

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.     

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.