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Three-dimensional Dose Verification Using Normoxic Polymer Gel Dosimeters for Tomotherapy Tung-Hsin1, Chien-Yi Hsiao2, Wu Mu-Bai Chang2, Geoffrey Zhang3, Ji-An Liang2, Tzung-Chi Huang2,* 1 Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan 2 Department of Biomedical Imaging and Radiological Science, China Medical University, Taiwan 3 Department of Radiation Oncology, Moffitt Cancer Center, Florida, USA *Corresponding author: Tzung-Chi Huang, Ph.D. 155 Li-Nong St., Sec. 2, Taipei, Taiwan 112 Tel: 886-4-22053366 Fax: N/A E-mail: [email protected] Abstract The aim of this study is to evaluate the feasibility of using MAGAT as a near real-time 3-dimensional dose measurement device for tomotherapy. MAGAT is a new type of normoxic polymer gel dosimeter, which responses well to absorbed dose and can be easily made in the presence of normal oxygen surroundings. Its dose response was measured by irradiating MAGAT-gel-filled testing vials with tomotherapy and its linear relationship with dose was present from 0 to 6.5 Gy. One group of gel samples were measured in near real-time, in which the gel phantom was read right after the irradiation. The other group was measured 12 hours after irradiation so the gel phantom can be exposed to oxygen. Several post-imaging processing filters including Nagao, Guess, median, mean, min and max, were applied on megavoltage computed tomography (MVCT) images for better discrimination on dose responses. Our results show that dose responses for MVCT with real-time and 12-hour delayed measurement were 4.76 and 4.69 ΔSI.cGy-1, respectively, and show no significant difference (p-value = 0.72). For study of the filtering effects, Gauss, median and mean filters offer better linear correction coefficients of dose response. In conclusion, the MAGAT polymer gel dosimeter read from MVCT imaging is a promising method for dose verification in clinical tomotherapy. Key Words: Dose Verification, Polymer Gel Dosimeters, Tomotherapy, Radiation dosimetry Introduction Tomotherapy delivers radiation using a rotating intensity-modulated fan beam geometry, and the modulation varies with gantry angle. Because the resultant dose-distributions comprise modulated contributions from many angles, the system has the potential to deliver highly conformal treatments. It was designed to be a purpose-built image guided radiotherapy (IGRT) machine. The capability for continuous rotation, coupled with translation of the patient through the gantry, allows helical treatment arcs in a way similar to helical or spiral diagnostic CT scanners. The helical tomotherapy accelerator is mounted on a slip ring gantry. This allowed a CT detector array (Xenon filled linear array) to be mounted opposite the source. The primary purpose of this detector is for megavoltage computed tomography (MVCT), delivery verification, and dose reconstruction [1,2]. This on-board linear array of ion chambers also has demonstrated its advantage for quality assurance and beam alignment commissioning [3]. Additionally, it has also proved useful for quantifying required dose planning parameters. The mostly used radiation dose measurement detectors in the clinics, including ion chamber, film and thermal-luminiscence detector (TLD), are often applied in 1- or 2-dimensional (1D or 2D) dose measurements. The gel dosimeter can measure 3-dimensional (3D) dose distribution directly. There are two categories of gel dosimeters, Fricke gel and polymer gel. Fricke gel was proposed and studied first for 3D dose measurement [4]. Due to its low dose sensitivity and small dose measurement range, Fricke gel has not been clinically used in radiotherapy dose measurement. Monomer molecules in a polymer gel dosimeter solution change to polymer molecules via polymerization after ionizing radiation irradiated. This polymerization process changes the solution to gum. The amount of such mononer-polymer conversion is proportional to the radiation dose within a certain dose range. Dose measurement is thus achieved by the assessment of the polymerization in the dosimeter. Normoxic polymer is an improved polymer gel, which can be made in room temperature [5]. MAGAT normoxic polymer has the characteristics of tissue equivalence and higher dose sensitivity [6]. Magnetic resonance imaging (MRI) has been the most widely used signal read out device in 3D gel dosimetry research [7]. Other related research applied kilo-voltage computed tomography (kVCT) [8-11] and kilo-voltage cone beam computed tomography (kVCBCT) systems [11] as signal readers for gel dose measurement. The aim of this study is to evaluate the feasibility of using MVCT as a near real-time measurement device in dose estimation for tomotherapy with normoxic polymer gel dosimetry. In order to eliminate higher noise level induced by MVCT high energy photons as compared to that of kVCT, various post-imaging processing filters including Nagao, Guess, median, mean, min and max , were also applied on MVCT images for better discrimination on dose responses. Materials and methods The clinical helical tomotherapy unit (TomoTherapy Inc., Madison, Wisconsin, USA) consists of a 6-MV linear accelerator with a binary multi-leaf collimator and a xenon CT detector system. The MVCT mode of the linear accelerator reduces the nominal energy to about 3.5 MV, and transverse 4-mm MVCT images were obtained. This results in the acquisition of volumetric images at acceptable doses, typically between 0.5 cGy and 3 cGy [12], which are comparable with doses required from planar images on contemporary MV electronic portal imaging devices (EPIDs). The MAGAT normoxic polymer gel was prepared under normal oxygen conditions using gelatin (porcine skin, type A, 300 Bloom, Sigma Aldrich), methacrylic acid (monomer purity > 98%, Sigma Aldrich), tetrakis hydroxyl methyl phosphonium choloride (THPC) solution (80% solution in water, Sigma Aldrich), as an oxygen scavenger, and distilled water (high performance liquid chromatography grade) (Table 1). The gelatin was given to distilled water and heated to 50°C in a water bath. A clear solution was achieved and cooled down to 35°C. The methacryliac acid and THPC solution were then added to the gelatin solution. A homogeneous liquid mixture was achieved by continuous stirring. All gels were prepared and poured into 60 ml plastic vials of 25 mm in diameter and 115 mm in height and filled to the top to minimize oxygen presence in the vials. A study has indicated that gels need to be exposed to oxygen for at least 12 hr after irradiation to terminate their intrinsic polymerization reactions and then kVCT can be used as a reading device [13]. This study examined effects on the timing of dose reading, including right after irradiation and 12 hours delay. Gel-filled vials were irradiated with uniform doses of 0–650 cGy with a step of 50cGy, using tomotherapy accelerator. MVCT was used to scan the samples to see signal changes in gel dosimeters. In the MVCT images of the gel samples after irradiation, higher grey levels correspond to higher radiation dose received. A region of interest (ROI) was delineated for each dose region and then was used to calculate individual signal intensity. The dose response was generated by the mean and standard deviation within each ROI of the MVCT image and mapped to known doses. R-square error from fitted linear function on dose response was analyzed for irradiated dose consistency. Dose response curves with different reading timing were measured and compared. The optimal timing of dose reading was determined by the analysis of the dose readings with different time delays. In terms of MVCT imaging, density changes resulted from high photon energy in gel were examined. Various filters including Nagao, Guess, median, mean, min and max filters were applied to the 3D MVCT images for diminution of imaging noise and better discrimination on dose responses. Results and Discussion Figure 1 shows dose response curves obtained with no time delay (real time) and 12-hour delay after irradiation, respectively, without use of filter. The difference in signal intensity linearly increased with the radiation dose. Linear fitting was applied to both sets of data with slope of 4.76 ΔSI.cGy-1 (real time) and 4.69ΔSI.cGy-1 (12-hour delay), respectively. No significant difference (p=0.72) was revealed with different reading timing, exhibiting the accuracy of dose response for real-time measurement. Figure 2 and Figure 3 demonstrate the difference between the calibration curves with different filters applied to the data set of real-time and 12-hour delay readings, respectively. In Figure 2, almost all similar dose response curves were obtained with a range of slope from 4.33 ΔSI.cGy-1 to 4.76 ΔSI.cGy-1. Data with Nagao, Gauss, median, mean, min and without filter showed no statistically difference (p=0.99), while that with max filter would induce substantially dose sensitivity reduction (p=0.01). Thus, interpreting data with max filter might be not suitable for MVCT gel dosimetry. Figure 3 shows dose response curves for 12-hour delay reading from 0 cGy to 650 cGy in testing various imaging filters. Likewise, the slopes of dose response curves were 4.69, 3.62, 4.51, 4.40, 4.44, 3.85 and 3.30 for without filter, with Nagao, Gauss, median, mean, max and min filter respectively, and no statistically difference was revealed (p=0.99). It is worth mentioning that dose response with max filter was similar to those with other filters. For both real-time and 12-hour delayed readings, Gauss, median and mean filters were found to be optimized for the calibration curve generation. MAGAT gel dosimeter has the advantages of 3D dose measurement, tissue equivalence, high dose sensitivity, easy preparation, low cost, capability of accumulative dose measurement and its signal is not spreading with time. However, one needs to be cautious in temperature and composition control in preparation to avoid hydrolysis and polymerization. Incomplete prepared gel dosimeter also affects the dose response. The dose delivered by the MVCT to the dosimeter is about 1% of a fractional dose in radiotherapy treatment. The additional dose from the MVCT scan is thus within the tolerance. The higher the dose absorbed by the dosimeter, the higher the attenuation to the MVCT photons by the gel. The response is linear to the absorbed dose within the dose range in radiotherapy. The tomotherapy unit is the dose delivering system and its MVCT is the dose reading system when MAGAT polymer dosimeter is used, which not only provides a robust treatment quality assurance system, but also warrants the measurement consistency. Conclusions In this work, we have investigated the dose response curves for MAGAT polymer gel dosimeter using tomotherapy as the dose delivering machine and its MVCT as the 3D dose reader. This study is the first attempt to explore the potential role of using MVCT as a reading device for gel dosimeters. The dose responses, measured at different MVCT imaging times, showed no significantly difference. For effects of different filters, Gauss, median and mean filters offer better linear correction coefficients of dose response. In conclusion, normoxic polymer gel dosimeter combined with MVCT as a dose reading device provides a useful method for tomotherapy in three-dimensional real-time dose measurement and verification. References 1. Ruchala J., Olivera G. H., Schloesser E. A., and Mackie T. R.,1999. Megavoltage CT on a tomotherapy system. Phys. Med. Biol. (44) 2597–2621. 2. Kapatoes M., Olivera G. H., Ruchala K. J., Reckwerdt P. J., Smilowitz J. S., Balog J. P., et al., 2001. A feasible method for clinical delivery verification and dose reconstruction in tomotherapy. Med. Phys. (28) 528–542. 3. Balog J., Mackie T. R., Pearson D., Hui S., Paliwal B., and Jeraj R., 2003. Benchmarking beam alignment for a clinical helical tomotherapy device. Med. Phys. (30) 1118–1127. 4. Gore, J.C, Kang, Y.S., and Schulz, R.J., et al.,1984. Measurement of radiation dose distributions by nuclear magnetic resonance imaging. Phys. Med. Biol. (29) 1189–1197. 5. De Deene, Y., Hurley, C., Venning, A., Vergote, K., Mather, M., Healy, B.J., et al., 2002. A basic study of some normoxic polymer gel dosimeters. Phys. Med. Biol. 47 (19), 3441–3463. 6. Hurley, C., Venning, A., Baldock, C., 2005. A study of a normoxic polymer gel dosimeter comprising methacrylic acid, gelatin and tetrakis (hydroxymethyl) phosphonium chloride (MAGAT). Appl. Radiat. Isot. 63 (4), 443–456. 7. Lee, J.S., Tsai, C.J., Lo, M.K., Huang, Y.H., Chen, C.C., Wu, J., Tyan, Y.S., et al. 2008. Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging. Nucl. Instrument Meth. B 266 (10), 2199–2202. 8. Hilts, M., Audet, C., Duzenli, C., Jirasek, A., 2000. Polymer gel dosimetry using X-ray computed tomography: a feasibility study. Phys. Med. 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Composition of 100ml MAGAT gel Chemical Concentration Gelatine 6%, 6 g Methacryic acid (MAA) 9%, 9 g THPC 10 mM Distilled water 85%, 85 ml 4000 3500 5000 3000 5000 4500 2500 Real-time ΔSI = 4.76.Dose + 0.13 R-square: 0.950 4500 4000 2000 4000 3500 12-hour delay ΔSI = 4.69 .Dose - 0.005 R-square: 0.954 1500 3500 3000 1000 3000 2500 ΔSI 500 2000 0 0 1500 200 2000 1000 1500 500 1000 0 0 100 2500 300 400 500 600 700 800 500 100 200 300 400 0 0 500 100 600 200 700 300 800 400 500 600 700 800 Dose (cGy) Figure 1. Dose response curves of real-time reading (●) and 12 hours delay reading (○). The horizontal axis is the absorbed dose in cGy, and the vertical axis is the MVCT signal intensity difference, ΔSI. 5000 Real time 4500 4000 3500 ΔSI 3000 2500 2000 1500 1000 500 0 0 100 200 300 400 500 600 700 800 Dose (cGy) Figure 2. Dose response curves for real-time reading with no filter(○) and with Nagao (□), Gauss (×), median (●), mean (+), max (*) and min (◊) filters. The horizontal axis is the absorbed dose in cGy, and the vertical axis is the MVCT signal intensity difference, ΔSI. 5000 4500 4000 3500 ΔSI 3000 2500 2000 1500 1000 500 0 0 100 200 300 400 500 600 700 800 Dose (cGy) Figure 3. Dose response curves for 12 hours delayed reading with no filter(○) and with Nagao (□), Gauss (×), median (●), mean (+), max (*) and min (◊) filters. The horizontal axis is the absorbed dose in cGy, and the vertical axis is the MVCT signal intensity difference, ΔSI.