|Year : 2015 | Volume
| Issue : 3 | Page : 580-585
Enhancing the longevity of three-dimensional dose in a diffusion-controlled Fricke gel dosimeter
S Ebenezer Suman Babu, I Rabi Raja Singh, CG Poornima, B Paul Ravindran
Department of Radiotherapy, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Web Publication||9-Oct-2015|
S Ebenezer Suman Babu
Department of Radiotherapy, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: The principle of Fricke gel dosimeter is the oxidation of ferric ions on exposure to radiation. The major limitation in this dosimeter is the post-irradiation diffusion of ferric ions leading to degradation of spatial dose information.
Aims and Objectives: The primary objective of this study is to reduce diffusion of ferric ions post-irradiation and enhance the spatial stability of the dose for an acceptable period, within which it can be read out.
Materials and Methods: A novel method has been proposed to achieve this aim by incorporation of an anti-oxidant in the present Fricke gel dosimeter. The modified gel prepared in this study consisted of 50 mM sulfuric acid, 0.05 mM xylenol orange, 0.5 mM ferrous ammonium sulfate, and an optimal concentration of anti-oxidant. Different concentrations of the anti-oxidant (ascorbic acid and glycine) based gel dosimeters were prepared. The performance evaluations of the same were characterized dosimetrically with high energy photons (x- and gamma rays). Spectrophotometric measurements of gel dosimeters were performed at a wavelength of 585 nm and the post-irradiation diffusion was studied by observing the dose response over time. The spatial dose information from the large volume cylindrical gel phantoms was acquired using an in-house optical computed tomography scanner.
Results: Auto-oxidation and diffusion were controlled in the enhanced Fricke gel dosimeter by the incorporation of glycine as anti-oxidant. The post-irradiation dose in the gel dosimeter was stable up to 6 hours, thereby enhancing the longevity of three-dimensional (3D) dose.
Conclusion: The widely established limitations of Fricke gel dosimeter viz., auto-oxidation and diffusion were overcome using a novel method that incorporated optimal quantity of glycine as a suitable anti-oxidant. This modified Fricke gel dosimeter could be used as an effective 3D dosimeter for practical applications in radiotherapy.
Keywords: Anti-oxidant in Fricke gel, controlling diffusion of ferric ions, Fricke gel dosimeter, longevity of three-dimensional dose, stability of spatial resolution in gel
|How to cite this article:|
Babu S E, Singh I R, Poornima C G, Ravindran B P. Enhancing the longevity of three-dimensional dose in a diffusion-controlled Fricke gel dosimeter. J Can Res Ther 2015;11:580-5
|How to cite this URL:|
Babu S E, Singh I R, Poornima C G, Ravindran B P. Enhancing the longevity of three-dimensional dose in a diffusion-controlled Fricke gel dosimeter. J Can Res Ther [serial online] 2015 [cited 2020 Aug 8];11:580-5. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/580/163689
| > Introduction|| |
Advancements in the field of radiation therapy have enriched the medical fraternity in the fight against cancer. Nevertheless, the high precision techniques employed in delivering the radiation dose, incorporate complex mechanisms for which simple calculations do not suffice. Therefore, we require a dosimetric system that is capable of providing the dose information in true three-dimensional (3D) form that will help the medical physicists and the radiation oncologists in the decision-making process with regard to the selection of the appropriate treatment plan. The idea of incorporating the Fricke solution into a gelatin matrix by Gore et al. gave the spark for the development of gel dosimetry. ,,
Gel dosimeter is an excellent tissue-equivalent dosimeter in the form of a phantom that helps determine the absorbed dose in a 3D geometry, thereby giving it the edge over conventional dosimeters such as ionization chamber, film, and the two-dimensional array detectors. These advantages are particularly important in the verification of dose distribution in intensity-modulated radiation therapy and stereotactic radiosurgery where steep dose gradients exist. In Fricke gel dosimeter, the ferrous (Fe 2+ ) ions present in ferrous ammonium sulfate (FAS) are spread throughout the gelatin matrix.  When irradiated, radiation-induced changes may occur in the gel matrix, and these changes correspond to dose absorbed.
The major limitation of Fricke gel dosimeter is the diffusion of ferric (Fe 3+ ) ions after irradiation which leads to the loss of spatial dose information captured by the gel matrix. Several research studies are being carried out to overcome this limitation. ,,, In this study, we propose a new Fricke gel dosimeter by incorporation of an optimal concentration of the anti-oxidizing agent to control the post-irradiation diffusion of absorbed dose.
| > Materials and methods|| |
Fricke gel preparation
The components of the Fricke gel dosimeter were gelatin 240/300 bloom (Sigma), FAS (S D Fine-Chem Limited), xylenol orange (Sigma-Aldrich) and sulfuric acid (Qualigens). Due to the commercial non-availability of conventionally used 300 bloom gelatin, all preliminary experiments were carried out with 240 bloom gelatin (S D Fine-Chem Limited) as bloom strength of gelatin does not affect the dose outcome from gel dosimeters. , The optimized concentration of anti-oxidant based gel recipe obtained from the above experiments was verified with 300 bloom gelatin to endorse the findings.
Initially, stock solutions of FAS, xylenol orange, and sulfuric acid were prepared. Gelatin solution was prepared by dissolving 5% by weight in triple-distilled water and stirring continuously for 1 hour using a magnetic stirrer at 45°C in a water bath. When the gelatin was completely dissolved, the temperature of the solution was cooled down to 25°C after which 1 M sulfuric acid, 0.05 mM xylenol orange, and 0.5 mM FAS were added from the stock solutions.
Development of enhanced Fricke gel dosimeter
In order to control post-irradiation diffusion, the original recipe was modified with the addition of different concentrations of anti-oxidizing agents viz., ascorbic acid and glycine. Initially, 100 mM ascorbic acid was added to the original recipe and stirred well for 5 min. The resulting solution was then transferred to cuvettes of 4 ml volume and 1 cm path length as shown in [Figure 1]. In order to arrive at the optimal concentration of anti-oxidant based Fricke gel dosimeter, different concentrations of ascorbic acid (Sigma) viz., 25, 12.5, 3.0, 0.6, 0.4, 0.3, 0.01, and 0.001 mM were added to the original recipe. Spectrophotometric measurements were performed for each concentration of the modified gel dosimeter, and the post-irradiation diffusion was studied by observing the dose response over time. Similarly, various concentrations of glycine (Sigma) based Fricke gel recipe were prepared and the post-irradiation diffusion was spectrophotometrically analyzed. To study the diffusion in large volume gel dosimeter (bulk gel), transparent plastic cylinders of one litre capacity were filled with the gel solution for dose measurements. All the gel samples were kept in the refrigerator for 4 hours at 4°C.
|Figure 1: Fricke gel dosimeter in optical cuvettes (4 ml volume) of 1 cm path length|
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Irradiation of gel cuvettes
Dose response measurements
The gel samples were irradiated in a water bath using a telecobalt unit (Theratron 780 C, Theratronics International Limited) with parallel opposed lateral beams of field size 35 cm × 35 cm. Perspex slabs of 10 cm thickness were kept below the water bath to account for backscatter as shown in [Figure 2]. The gel cuvettes were irradiated with different doses ranging from 0 to 20 Gy.
Dose rate and energy dependence
In order to study the dose rate dependence of the modified Fricke gel dosimeter, the gel samples were also irradiated at different dose rates ranging from 100 to 600 MU/min, in steps of 100, on the dual energy linear accelerator (Clinac 2100 C/D, Varian Medical Systems, USA). Further, the influence of energy on the new gel dosimeter was analyzed by irradiating the gel samples with 6 and 15 MV x-rays, respectively.
Irradiation of cylindrical gel phantom
The cylindrical gel phantom was irradiated with a narrow beam of x-rays using a stereotactic circular cone of diameter 1 cm, attached to the collimator head of the linear accelerator to deliver a dose of 3 Gy. Prior to irradiation of the gel dosimeter, a pre-scan of the phantom was acquired using an in-house optical computed tomography (CT) scanner consisting of an aquarium with a turn-table, a matrix of yellow LEDs as light source, a band pass filter and a high resolution camera (1024 × 768 pixel matrix, Point Gray FlyCapture camera) as a detector as shown in [Figure 3]. The schematic representation of the optical CT read-out process is shown in [Figure 4]. The performance evaluation of the in-house optical CT scanner used in this study has already been investigated and established. 
|Figure 3: Setup of optical computed tomography scanner read out system for scanning large volume (bulk gel) phantoms|
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|Figure 4: Schematic representation of optical computed tomography scanner setup for read out of gel|
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Evaluation of gel dosimeters
The irradiated gel samples in cuvettes were evaluated using a spectrophotometer (UV-1800, Schimadzu, Japan) at a wavelength of 585 nm. Also, pre- and post-irradiation scans of the bulk gel in the cylindrical phantom were performed to find the diffusion property when the gel dosimeter exists as a large volume. The post-irradiation diffusion readings were taken hourly, up to 6 h, and randomly up to 33 h. The axial beam profile from the cylindrical phantom was reconstructed using software coded in MATLAB (Math Works, Inc., USA) employing subtraction of pre-irradiation scan data from the post-irradiation scan data. In all the cases, the unmodified original recipe of the Fricke gel dosimeter (without anti-oxidant) was taken as the reference to aid comparison.
| > Results|| |
In this study, a newly modified gel dosimeter consisting of 50 mM sulfuric acid, 0.5 mM FAS, 0.05 mM xylenol orange, and 0.3 mM glycine has been developed. From the results, it was found that the gel dosimeter prepared by the incorporation of an optimal concentration of glycine (0.3 mM) anti-oxidant was able to hold the 3D dose information upto 6 hours from the time of irradiation (post-irradiation) as shown in [Figure 5]. The new gel dosimeter was found to be independent of the energy of the radiation used as shown in [Figure 6]. The reconstructed images of the gel phantom demonstrating the diffusion control ability of the modified gel dosimeter are shown in [Figure 7]. The comparison of axial beam profiles of 3 rd , 6 th , 7 th , and 11 th hour post-irradiation scans obtained from the reconstructed images is shown in [Figure 8].
|Figure 5: Dose response of 0.3 mM glycine incorporated Fricke gel dosimeter and the diffusion w.r.t. time|
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|Figure 6: Energy dependence of the new gel dosimeter for 6 MV and 15 MV photons|
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|Figure 7: MATLAB reconstructed images of the single circular photon beam irradiation on gel phantom demonstrating spatial stability and the diffusion control ability of 0.3 mM glycine incorporated Fricke gel dosimeter|
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|Figure 8: Comparison of 3 h, 6 h, 7 h, and 11 h profiles from reconstructed images of gel demonstrating the diffusion control in the enhanced Fricke gel dosimeter|
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The 3 rd hour post-irradiation isodose distributions were compared with the 6 th , 7 th and 11 th hour isodose distributions as shown in [Figure 9],[Figure 10] and [Figure 11], respectively.
Prior to arriving at the optimal concentration of glycine-based Fricke gel dosimeter, various concentrations of ascorbic acid-based gel dosimeters were also analyzed. The response of the dosimeter with 100 mM ascorbic acid showed complete control over the auto-oxidation process. Additionally, various concentrations of ascorbic acid viz., 25 mM, 12.5 mM, and 3 mM, respectively showed similar optical densities. However, there was no dose response in the gel samples prepared with the above concentrations of ascorbic acid. The dose response of gel prepared with 3 mM concentration of ascorbic acid is illustrated in [Figure 12].
|Figure 12: Dose response and diffusion control for 3 mM ascorbic acid added Fricke gel dosimeter|
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When the gel samples were prepared with low concentrations of ascorbic acid, they were sensitive to dose but the diffusion was prominent in measurements around 2 h post-irradiation. Due to the unresponsiveness to dose, the higher concentrations of ascorbic acid were lowered to 0.001 mM, 0.01 mM, 0.1 mM, 0.3 mM, 0.45 mM, and 0.6 mM, respectively. While the concentrations of the anti-oxidant (0.001 mM and 0.01 mM and 0.1 mM) were sensitive to dose, they could not control the diffusion within the Fricke gel dosimeter. It was also observed that the auto-oxidation that had crept into the gel samples affected the dose response of gels with 0.3 mM, 0.45 mM, 0.6 mM concentrations of ascorbic acid. Since it was evident that no concentration of ascorbic acid was suitable in controlling both diffusion and auto-oxidation, glycine was investigated as an alternative anti-oxidant.
The 10 mM glycine-incorporated Fricke gel dosimeter, which was found to be highly insensitive to dose (3%), exhibited mild diffusion. However, auto-oxidation of the Fe 2+ ions could be controlled in this formulation of the gel. On the other hand, 0.3 mM glycine incorporated gel dosimeters showed linear dose response upto 10 Gy along with the diffusion arrested for 6 hours and 5% diffusion upto 33 hours after irradiation.
| > Discussion|| |
The concentration of ferric ions in the gel dosimeter corresponds to the radiation dose absorbed in it, and this can be quantified by measurement of Fe 3+ ions present.  The reconversion of ferric ions to Fe 2+ ions contributes to the diffusion of the spatial dose distribution and limits the use of the present Fricke gel dosimeter. Further, the auto-oxidation reduces the transparency of the dosimeter as it becomes darker with increasing time between the gel preparation and irradiation.
Baldock et al. experimentally determined the diffusion co-efficient of ferrous sulfate gels.  The concern of diffusion could be practically addressed in terms of the time interval between irradiation and read out of dose distributions from the irradiated gel dosimeters.  Though few investigators have given a time scale ranging from 30 min to 2 h post-irradiation for reading the gel dosimeter by the addition of chelators (anti-oxidant), the effect of this addition also altered the dose sensitivity. , A new approach, by Silva et al. who added polyethylene honeycomb structure for controlling diffusion,  may not be convenient for optical imaging due to the scatter component associated with it.  In practice, this disadvantage can be overcome by prompt dosimeter analysis and strongly constraining the time between irradiation and analysis. 
Contrary to the above studies, the approach to add an anti-oxidant directly to the existing Fricke gel recipe has not been extensively studied thus far. According to the IUPAC definition, chelate refers to the formation of two or more co-ordinate bonds between the ligand and the single central atom.  As chelators can provide co-ordination bonds with the Fe 3+ ion, the degradation of spatial dose information due to ion diffusion can be controlled. On this basis, amino acids such as ascorbic acid and glycine were taken for investigation in this study.
Mechanism of action of glycine
The amino acid being the chelate in this study was expected to provide the stability to the Fe 3+ ions after irradiation by forming a co-ordinate bond with it. Glycine forms a stable 1:1 complex in an acidic solution. The chemical stability of Fe 3+ ions in the presence of glycine in solutions has been reported in literature. , Since the Fricke gel dosimeter contains sulfuric acid as one of the ingredients provided the acidic medium, the stability of Fe 3+ ions produced upon irradiation was held in the gel matrix without undergoing the problem of diffusion.
0.3 mM concentration of glycine returned a favorable response in terms of controlling diffusion post-irradiation as well as reducing the auto-oxidation of Fe 2+ ions before and after irradiation. The spatial dose distribution in the bulk gel phantom was stable for more than 6 h. This enables the user to have the convenience of extended time available for reading the dose from the gel as compared to the current read-out time limit of 2 hours post-irradiation. Based on these results, it is recommended that an optimal concentration of 0.3 mM glycine could be used in the Fricke gel dosimeter for practical, convenient and effective use of gels in the routine verification of 3D dose distributions. Gel samples prepared with 0.5 mM concentration of glycine were also investigated and found to have properties similar to the 0.3 mM glycine with 1% reduction in the dose response.
In the present study, 0.001-0.3 mM ascorbic acid in the gel dosimeter did not produce the expected control of diffusion as auto-oxidation was more prominent in the gel samples. Increasing the concentration of anti-oxidant in the gel formulation from 0.3 mM viz., 0.45 mM, 0.6 mM, 3 mM, 12.5 mM, 25 mM, and 100 mM suppressed the auto-oxidation but at the cost of dose sensitivity of the gel dosimeter, making it unusable. The modifications in the recipe with 10 mM glycine did not solve this problem as it succeeded in reducing the auto-oxidation of Fe 2+ ions in the gel but failing to deliver in terms of dose response.
| > Conclusion|| |
The longevity of spatial dose distribution in the gel dosimeter has been achieved successfully by incorporating glycine as the anti-oxidant, thereby suppressing both auto-oxidation and diffusion in the Fricke gel dosimeter. The post-irradiation measurements showed the endurance of the spatial dose up to 6 hours while maintaining dose sensitivity of the dosimeter. The addition of ascorbic acid as anti-oxidant did not produce the expected result as the sensitivity of the gel dosimeter was significantly affected with the increase in the concentration of the anti-oxidant. Therefore, from this study, it is concluded that the diffusion in Fricke gel dosimeter could be controlled by adding glycine which provides a convenient period for reading the gel dosimeter post-irradiation. This enhanced Fricke gel dosimeter which overcomes the limitations of its predecessors, promises to be a valuable 3D dose verification tool for radiation therapy quality assurance.
The authors would like to thank the Institutional Review Board of Christian Medical College, Vellore for funding this study, Mr. Timothy Peace, Lecturer, Department of Radiotherapy, Christian Medical College, Vellore and Mr. Suresh Kumar, Scientist, ISRO, Thiruvananthapuram for the useful discussions.
Financial support and sponsorship
Institution Review Board, Christian Medical College, Vellore.
Conflicts of interest
There are no conflicts of interest.
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