Dosimetric characteristics of intensity-modulated radiation therapy and RapidArc therapy using a 3D N-isopropylacrylamide gel dosimeter

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Applications of Nuclear Techniques (CRETE15) International Journal of Modern Physics: Conference Series Vol. 44 (2016) 1660221 (9 pages) The Author(s) DOI: 10.1142/S2010194516602210 Dosimetric characteristics of intensity-modulated radiation therapy and RapidArc therapy using a 3D N-isopropylacrylamide gel dosimeter Chun-Hsu Yao * Department of Biomedical Imaging and Radiological Science / School of Chinese Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung City, Taiwan 40402, R.O.C. Department of Biomedical Informatics, Asia University, 500, Liufeng Rd., Wufeng, Taichung City, Taiwan 41354, R.O.C. chyao@mail.cmu.edu.tw Ting-Yu Tsai * Department of Biomedical Imaging and Radiological Science, China Medical University No.91, Hsueh-Shih Road, Taichung City, Taiwan 40402, R.O.C. bonheur524@gmail.com Bor-Tsung Hsieh Department of Biomedical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, No.666, Buzih Road, Beitun District, Taichung City, Taiwan, R.O.C. bthsieh@ctust.edu.tw Yuk-Wah Tsang, Chung-Yu Chiu and His-Ya Chao Department of Radiation Oncology, Ditmanson Medical Foundation Chiayi Christian Hospital, No.539, Zhongxiao Rd., East Dist., Chiayi City, Taiwan 60002, R.O.C. 07130@cych.org.tw Yuan-Jen Chang Department of Management Information Systems, Central Taiwan University of Science and Technology, No.666, Buzih Road, Beitun District, Taichung City, 40601, R.O.C. ronchang@ctust.edu.tw Published 1 September 2016 This study aimed to investigate the dosimetric characteristics of intensity-modulated radiation therapy (IMRT) and RapidArc therapy by using 3D N-isopropylacrylamide (NIPAM) polymer gel. Optical computed tomography, specifically OCTOPUSTM-10X fast optical computed tomography scanner, was used as a readout tool. Two cylindrical acrylic phantoms (10 cm in diameter, 10 cm in height, and 3 mm in thickness) were filled with NIPAM gel and used for IMRT and RapidArc irradiation by using the Clinac ix treatment machine. The irradiation energies for * These authors contributed equally to this work. Corresponding author This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 3.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited. 1660221-1

C. H. Yao et al. IMRT and RapidArc were set as 6 MV photons, but their irradiation angles and dose rates differed during irradiation. The irradiation angles of IMRT were 120, 155, 180, 215, and 245, and the dose rate was fixed at 400 cgy/min. RapidArc rotated continuously during irradiation, and the dose rate varied from 330 cgy/min to 400 cgy/min. The pass rates were 98.02% and 97.48% for IMRT and RapidArc, respectively, and the rejected area appeared at the edge of the irradiated region. The isodose lines of IMRT and RapidArc were consistent with those of TPS in most regions. Scattering and edge enhancement effects are main factors that cause dose inaccuracy in the edge region and reduced pass rates. Considering dose rate dependence, we used variable dose rates during irradiation with RapidArc. Results showed that the dose distribution of NIPAM gel was consistent with that of TPS. The pass rates were also the same for IMRT and RapidArc irradiation. This study proposes a preliminary profile of dosimetric characteristics of IMRT and RapidArc by using a NIPAM gel dosimeter. Keywords: NIPAM gel dosimeter; Optical CT; IMRT; RapidArc. 1. Introduction Intensity-modulated radiation therapy (IMRT) has been widely adopted for clinical use because it can generate dose distributions that precisely conform to the tumor target while minimizing the dose delivered to the surrounding healthy tissues. 1 However, IMRT requires high monitoring units and long treatment times. RapidArc (Varian Medical Systems), a novel radiation treatment technique, is based on volumetric-modulated arc delivery and differs from intensity modulation, which uses fixed gantry beams. The treatment time of RapidArc is four to eight times faster than IMRT. 2 The complex 3D dose distribution generated by RapidArc is difficult to verify using conventional techniques, such as a 1D ion chamber or 2D detector. Therefore, a true 3D dosimeter must be developed to verify the dose distribution. Polymer gel dosimeters show great potential for verification of dose distribution because of their ability to record true 3D dose distribution in the entire volume. 3 Although the first gel dosimeter, which used radiation-induced color change, was first proposed in 1950, 4 it only began to attract attention in the 1990s. Many gel formulations have been developed, including polyacrylamide gel, methacrylic and ascorbic acid in gelatin initiated by copper, BANG, and N-isopropylacrylamide (NIPAM). 5 10 NIPAM gel dosimeters exhibit low toxicity, high linearity, high sensitivity, and easy benchtop preparation without requiring a glove box. 11 13 In addition, NIPAM gel dosimeters present high spatial stability and can retain the dose distribution between 24 and 72 h post-irradiation. Previous studies found that an edge enhancement effect was observed around a 4 cm 4 cm irradiation region at 72 h post-irradiation. 14 Dose overestimates at the highdose gradient region may result in higher deviation at 72 h post-irradiation. Dose deviation increased with increasing post-irradiation time. A 3D polymer gel dosimeter has been employed to verify the dose distribution of RapidArc. The results showed that within isodose volumes of 80% and 95%, the dose deviation was less than 5% for 90% of the voxels between the calculated and measured dose distributions. 15 In 2014, Hayashi et al. used three types of dosimeters, namely, MapCHECK diode array detector, radiochromic EBT2 films, and BANG3 RPGD, to verify RapidArc TPS for irradiation of patients with prostate cancer. 16 The results indicated that the BANG3 RPGD dosimeter 1660221-2

Dosimetric characteristics of IMRT and RapidArc showed discrepancies between calculated and measured doses, particularly in low regions outside the target volume. Further improvement of the BANG3 RPGD dosimeter is thus needed. In this study, IMRT with constant dose rate and RapidArc with variable dose rate were used to verify the dose deviation between the calculated and measured dose distribution. 2. Materials and Methods 2.1. NIPAM polymer gel preparation NIPAM polymer gel is comprised of 5% gelatin, 5% NIPAM, 3% N,N -methylene bisacrylamide, and 5 mm Tetrakis (hydroxymethyl) phosphonium chloride. 10 Two cylindrical acrylic phantoms (10 cm in diameter, 10 cm in height, and 3 mm in thickness) filled with NIPAM gel were used for IMRT and RapidArc irradiation. The gel was placed in a water bath and cooled in a refrigerator for at least 6 h until solidification to reduce deviation in dose distribution. 11 NIPAM gel polymerization required 24 h to achieve dose stability after irradiation. 14 2.2. Treatment planning and irradiation Two irradiation treatment plans of IMRT and RapidArc were generated using the Eclipse planning system (Varian Corporation, Palo Alto, CA, USA). The irradiation energies for IMRT and RapidArc were set as 6 MV photons, but their irradiation angles and dose rates differed during irradiation. The irradiation angles of IMRT were 120, 155, 180, 215, and 245, and the dose rate was fixed at 400 cgy/min. RapidArc rotated continuously during irradiation, and the dose rate varied from 330 cgy/min to 400 cgy/min. The irradiation conditions for IMRT and RapidArc were as follows: source surface distance = 96 cm, irradiation depth = 4 cm, and prescribed dose = 5 Gy. 2.3. Dose-reading tool and data analysis After irradiation, polymerization occurred in the NIPAM gel and required 24 h to achieve dose stability. 14 A post-scan was performed through optical computed tomography (CT) using an OCTOPUSTM-10X fast optical CT scanner. 17 After scanning, images were reconstructed using the filtered back-projection algorithm with the program reconqexp.m integrated in MATLAB. Multiple slices were stacked to generate a three-dimensional image of dose distribution. A quantitative evaluation was performed using a gamma analysis technique, as proposed by Low et al. 18 Gamma index and pass rate were calculated point by point by comparing the dose distribution between TPS and measured data from the gel dosimeter. The criterion for gamma evaluation was 3% dose difference and 3 mm dose-to-agreement. Pass rate was calculated from the percentage of points with γ < 1.00. 18 1660221-3

C. H. Yao et al. 3. Results and Discussion Reconstructed images of both gel phantoms at the same depth are presented in Fig. 1. The images on the top row are the results of IMRT, and the images on the bottom row are the results of RapidArc. The images from left to right are non-irradiated gel, irradiated gel, TPS image, and subtraction of irradiated gel and non-irradiated gel. Based on the reconstruction image, consistent dose distribution was achieved by RapidArc (Fig. 1). However, RapidArc with various dose rates during irradiation exhibited certain challenges to the gel dosimeter, especially at the high-dose gradient area. Fig. 1. Reconstructed images of both gel phantoms. The images on the top row are the results of IMRT, whereas the images on the bottom row are the results of RapidArc. Left to Right: non-irradiated gel, irradiated gel, TPS image, and subtraction of irradiated gel and non-irradiated gel. 3.1. Non-irradiated gel spatial uniformity Prior to irradiation, the NIPAM gel was scanned to obtain a reference 3D image. The spatial uniformity of the gel phantom indicates the quality of gel preparation and the stability of the measurement system. Seven different depths of transverse slices (10, 20, 30, 40, 50, 60, and 70 mm) were used to evaluate spatial uniformity. We used standard deviation (SD) to estimate the dispersion of optical density at each location between different depths. 19 Low SD values were observed at every location, and the average SD of spatial uniformity for two non-irradiated NIPAM gels were as low as 0.14% and 0.12%. Therefore, both NIPAM gel phantoms were considered homogeneous between different depths and exhibited spatial uniformity. These results are similar to previously reported values. 20 3.2. Gamma evaluation After scanning, gamma evaluation was performed between TPS and the measured dose map by using optical CT. Figure 2 presents the comparison of the measured NIPAM gel 1660221-4

Dosimetric characteristics of IMRT and RapidArc dose distribution and TPS. The gamma index was calculated using a 3% dose difference and 3 mm distance to agreement, which are the most frequently used criteria in published comparisons of treatment plans. The gamma pass rate was calculated in the area percentage with γ < 1. Table 1 shows the gamma pass rate for IMRT radiation at different depths and post-irradiation times. The maximum pass rate is 98.02%, and the minimum pass rate is 91.8%. Table 2 shows the gamma pass rate for RapidArc radiation at different depths and post-irradiation times. The maximum pass rate is 97.48%, and the minimum pass rate is 89.02%. The dose distribution is stable from 24 h to 96 h post-irradiation, as indicated by the same level of gamma pass rates at different depths. The gamma pass rates of IMRT and RapidArc radiation are also on the same level. Nevertheless, the gamma pass rate of RapidArc radiation is lower than that of IMRT radiation at a depth of 40 mm. For further investigation, a gamma map of the rejected area (γ > 1) at a depth of 40 mm for 24 h to 96 h post-irradiation time is shown in Fig. 2. The most rejected area (γ > 1) is evidently located at the edge of the irradiated field. Apparently, the rejected area in RapidArc is larger than that in IMRT radiation, which explains the lower gamma pass rate of RapidArc radiation than that of IMRT radiation. The regions at the edge of the radiation field are generally high-dose gradient regions, which may probably induce the edge enhancement effect. 14 A dose is considered to be overestimated if edge enhancement phenomenon occurred, resulting in reduced gamma pass rate. Additionally, from Fig. 1 we found that the PTV shape of RapidArc radiation is more complex than that of IMRT radiation. It may probably cause the lower gamma pass rate for RapidArc radiation. More experiments will be conducted on the same PTV shape of RapidArc radiation and IMRT radiation. Table 1. IMRT gamma pass rate under 3%/3 mm criteria. Depth (mm) 30 35 40 45 50 24 h 94.13% 93.60% 92.14% 93.28% 95.29% 48 h 94.29% 92.13% 94.05% 97.95% 95.27% 72 h 92.35% 94.22% 93.18% 97.36% 97.74% 96 h 93.39% 93.27% 91.80% 98.02% 97.45% Table 2. RapidArc gamma pass rate under 3%/3 mm criteria. Depth (mm) 30 35 40 45 50 24 h 93.83% 93.09% 89.02% 94.73% 96.44% 48 h 91.63% 90.46% 89.77% 93.43% 97.48% 72 h 92.87% 91.65% 89.41% 93.91% 96.99% 96 h 91.67% 89.94% 89.73% 93.33% 94.82% 1660221-5

C. H. Yao et al. Depth = 40 mm Post irradiation time = 24 h IMRT 40 mm RapidArc 40 mm Fig. 2. Gamma map of the NIPAM gel dosimeter at a depth of 40 mm for 24 h post-irradiation time. 3.3. Isodose line The superimposed dose distributions at prescribed doses of 50%, 60%, 70%, 80%, 90%, and 100% are shown in Fig. 3 to determine differences in the dose distribution of the treatment planning system and measured data from NIPAM gel. The solid line indicates the treatment planning calculation, and the dotted line represents the measured data from the gel dosimeter. The results show good agreement between treatment planning and measured data. Xu et al. claimed that for a gel dosimeter, the dose distribution is only valid in the central region with 75% of the diameter of the gel container 21,22 because the 1660221-6

Dosimetric characteristics of IMRT and RapidArc optical density is affected by the reflection and refraction of the laser beams between the gel and the container wall. Similar phenomena can be found in the current work. We observed higher differences between treatment planning and measured data in the region at the 50% isodose line. Furthermore, the mismatch of dose distribution may be caused by the edge enhancement effect from the high-dose gradient (Fig. 3). Depth = 40 mm IMRT 40 mm RapidArc 40 mm Post irradiation time = 24 h Fig. 3. Superimposed dose distributions at the 50%, 60%, 70%, 80%, 90%, and 100% isodose lines at depth = 40 mm. Solid line: Treatment planning calculation, Dotted line: measured data from gel dosimeter. 1660221-7

C. H. Yao et al. 3.4. Temporal stability The pass rate of NIPAM gel slightly fluctuates from 24 h to 96 h (Table 1). The NIPAM (5-5-3-5) gel of RapidArc presents temporal stability despite minimal variations in dose rate. The current results are consistent with those in previous studies. 14 3.5. Projection image profile The reconstructed image of the NIPAM gel in the axial direction and projection data were processed using ImageJ (version 1.43, developed by the National Institutes of Health). Figure 4 shows the reconstructed image of the radiated gel phantom at 24 h postirradiation and the central line profiles. The reconstructed images of IMRT and RapidArc represent the subtractions of the irradiated gel and the reference gel images. Both gel phantoms exhibit the same maximum optical density, but from the line profiles, we could observe small peaks at the edge of the radiation region for RapidArc irradiation. Therefore, the effects of scattering and edge enhancement are more serious on the gel phantom with RapidArc irradiation than that on IMRT. These effects may be caused by the variable dose rate for RapidArc irradiation, considering the problem of dose rate dependence. However, more experiments are needed to confirm this finding. (a) (b) Fig. 4. Reconstructed image of the NIPAM gel dosimeter and central line profile. (a) IMRT; (b) RapidArc. 4. Conclusion A NIPAM gel dosimeter combined with an optical CT scanner was applied on IMRT (dose rate fixed at 400 cgy/min) and RapidArc therapy (various dose rates ranging 1660221-8

Dosimetric characteristics of IMRT and RapidArc from 330 cgy/min to 400 cgy/min) to investigate the dosimetric characteristics. The NIPAM gel dosimeter exhibited spatial uniformity for different batch preparations. The gamma pass rates were on the same level for both IMRT and RapidArc irradiation. Moreover, the isodose line showed good agreement between TPS and measured data from the gel dosimeter. When the central line profile between IMRT and RapidArc was compared, a small peak can be observed at the edge of the irradiated region for RapidArc. This small peak was caused by the scattering and edge enhancement effect and could be the main reason for the reduction of the gamma pass rate. NIPAM gel under a small variable dose rate irradiation would not significantly affect the performance of a NIPAM gel dosimeter. Further experiments using larger dose rate variations must be performed to verify the effects of dose rate dependence on NIPAM gel dosimeters. Acknowledgments This study was financially supported by the Ministry of Science and Technology of Taiwan (MOST 103-2314-B-166-001-). References 1. N. Lee, D. Puri, A. I. Blanco and K. S. Chao, Head Neck 29, 387 (2007). 2. VMAT / RapidArc, Volumetric Arc Therapy, https://www.varian.com/oncology/treatmenttechniques/external-beam-radiation/vmat. 3. C. Baldock et al., Phys. Med. Biol. 55, R1 63 (2010). 4. C. Baldock, J. Phys. Conf. Ser. 56, 14 (2006). 5. M. J. Maryanski, Y. Z. Zastavker and J. C. Gore, Phys. Med. Biol. 41, 2705 (1996). 6. P. M. Fong, D. C. Keil, M. D. Does and J. C. Gore, Phys. Med. Biol. 46, 3105 (2001). 7. R. J. Senden, Phys. Med. Biol. 51, 3301 (2006). 8. B. T. Hsieh, Y. J. Chang, R. P. Han, J. Wu, L. L. Hsieh and C. J. Chang, J. Radioanal. Nucl. Ch. 290, 141 (2011). 9. Y. J. Chang, B. T. Hsieh and J. A. Liang, Nucl. Instrum. Meth. A 652, 783 (2011). 10. Y. J. Chang and B. T. Hsieh, PLoS One 7, 1 8 (2012). 11. B. T. Hsieh, J. Wu and Y. J. Chang, IEEE Trans. Nucl. Sci. 60, 560 (2013). 12. C. H. Yao et al., J. Phys. Conf. Ser. 444, 012030 (2013). 13. C. H. Yao et al., J. Med. Biol. Eng. 34, 327 (2014). 14. Y. J. Chang, C. H. Chen and B. T. Hsieh, J. Radioanal. Nucl. Ch. 301, 765 (2014). 15. S. Ceberg et al., J. Phys. Conf. Ser. 164 (2009). 16. N. Hayashi, R. L. Malmin and Y. Watanabe, J. Radiat. Res., 1 (2014). 17. Y. Xu and C. S. Wuu, Phys. Med. Biol. 58, 479 (2013). 18. D. A. Low, B. H. William, S. Mutic, and A. Purdy James, Med. Phys. 25, 656 (1998). 19. D. C. Montgomery, Design and Analysis of Experiments, 6th edn. (John Wiley & Sons, New York, 2005). 20. Y. J. Chang, J. Q. Lin, B. T. Hsieh, C. H. Yao and C. H. Chen, Radiat. Phys. Chem. 104, 192 (2014). 21. Y. Xu, C. S. Wuu, and M. J. Maryanski, Med. Phys. 31, 3024 (2004). 22. C. S. Wuu and Y. Xu, Med. Phys. 33, 1412 (2006). 1660221-9