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INSTITUTE OF PHYSICS PUBLISHING Phys. Med. Biol.

50 (2005) 36693679

PHYSICS IN MEDICINE AND BIOLOGY

doi:10.1088/0031-9155/50/16/002

A technique for respiratory-gated radiotherapy treatment verication with an EPID in cine mode
Ross I Berbeco, Toni Neicu, Eike Rietzel, George T Y Chen and Steve B Jiang
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA E-mail: rberbeco@partners.org

Received 28 February 2005, in nal form 11 May 2005 Published 28 July 2005 Online at stacks.iop.org/PMB/50/3669 Abstract Respiratory gating based on external surrogates is performed in many clinics. We have developed a new technique for treatment verication using an electronic portal imaging device (EPID) in cine mode for gated 3D conformal therapy. Implanted radiopaque ducial markers inside or near the target are required for this technique. The markers are contoured on the planning CT set, enabling us to create digitally reconstructed radiographs (DRRs) for each treatment beam. During the treatment, a sequence of EPID images can be acquired without disrupting the treatment. Implanted markers are visualized in the images and their positions in the beams eye view are calculated offline and compared to the reference position by matching the eld apertures in corresponding EPID and DRR images. The precision of the patient setup, the placement of the beam-gating window, as well as the residual tumour motion can be assessed for each treatment fraction. This technique has been demonstrated with a case study patient, who had three markers implanted in his liver. For this patient, the intra-fractional variation of all marker positions in the gating window had a 95% range of 4.8 mm in the SI direction (the primary axis of motion). This was about the same (5 mm) as the residual motion considered in the planning process. The inter-fractional variation of the daily mean positions of the markers, which indicates the uncertainty in the set-up procedure, was within +8.3 mm/4.5 mm (95% range) in the SI direction for this case.

1. Introduction Tumours in the abdomen and thorax often move due to respiration (Langen and Jones 2001, Weiss et al 1972, Suramo et al 1984, Davies et al 1994, Balter et al 1996, Shimizu et al 1999, Bryan et al 1984, Ross et al 1990, Ekberg et al 1998). The expansion of
0031-9155/05/163669+11$30.00 2005 IOP Publishing Ltd Printed in the UK 3669

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margins to accommodate for motion leads to greater irradiation of normal tissues than for static tumours. To mitigate the effect of motion, many treatment methods have been proposed or are in current clinical usage (Ohara et al 1989, Minohara et al 2000, Kubo and Hill 1996, Keall et al 2001, Mageras et al 2001, Maruhashi et al 1992, Mageras and Yorke 2004, Vedam et al 2001, Zhang et al 2003, Shirato et al 2000, Wong et al 1999, Berbeco et al 2004a, Schweikard et al 2000). In respiratory gating, surrogates of tumour location are used to trigger the therapeutic beam. Shirato et al have established a method for gating based on the three-dimensional location of a ducial implanted near the tumour. Continuous multi-view uoroscopy assures the user that the radiation is being delivered accurately. Schweikard et al used infrared external markers and implanted radiopaque markers to periodically reestablish the internal/external correlation throughout a Cyberknife system (Accuray, Inc, Sunnyvale, CA USA) irradiation session (Schweikard et al 2000). Berbeco et al have suggested the use of uoroscopic images for gating based on organ motion induced intensity variations and template-matching, without the use of implanted surrogates (Berbeco et al 2004a). Wong et al pioneered spirometry as a surrogate for tumour location (Wong et al 1999). Many institutions have also worked to develop techniques for respiratory gating based on the position of an external surrogate (or a collection of them) placed on the thorax and/or abdomen (Kubo and Hill 1996, Vedam et al 2001, Kubo et al 2000, Ozhasoglu and Murphy 2002, Ramsey et al 1999). The strategies that do not use internal anatomy monitoring during the treatment have a built-in assumption that the correlation between the surrogate and the tumour is known and does not change in an unpredictable way throughout the course of treatment. The correlation between these surrogates and internal anatomy is the source of much research and debate (Schweikard et al 2004, Koch et al 2004, Starkschall et al 2004, Tsunashima et al 2004, Vedam et al 2003, Ahn et al 2004, Hoisak et al 2004). If the correlation is not repeatable, or is not predictable, then some method of online or ofine monitoring of the treatment should be used to ensure the proper placement of the dose. The purpose of this study is not to prove or disprove the internal/external correlation, but to present an idea for a clinical tool that may be used for quality assurance of external signal based gated treatment. Ford et al developed a method for determining the residual motion by manually triggering the EPID during treatment and nding the location of the diaphragm (Ford et al 2002). The technique described in this paper improves upon this idea. Our method has been developed for retrospective analysis, but in the future it may be applied in real time for online verication of gated treatment. 2. Methods and materials 2.1. Treatment planning A case study is presented to illustrate the basic features of our method for gated treatment verication. The patient was a 72 year old male with a large liver tumour. Three gold cylindrical radiopaque seeds, 0.8 mm in diameter and 3 mm in length, were implanted at the left, right and inferior borders of the tumour, respectively. The seeds were implanted with their long axis roughly aligned with the patients SI axis for maximum visibility from angles orthogonal to this axis. The tumour motion was assessed during a uoroscopic simulation and was found to be mostly cranialcaudal with an amplitude of 2 cm peak to peak. The patient underwent a 4DCT scan under video breath coaching conditions (Rietzel et al 2004, Pan et al 2004). The resorted CT data sets also showed a 2 cm peak-to-peak motion of the markers. From the analysis of the 4DCT data set, the gating window was determined and the end-of-exhale CT set was chosen for treatment planning. A ve-eld coplanar 3D conformal

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Table 1. The treatment parameters and image statistics for the sample treatment. The data shown for each eld is: gantry angle, beam energy, dose per treatment fraction, number of images obtained from within the beam-on gate per treatment fraction, total number of good images, and average number of seeds visible in each image. Field 1 2 3 4 5 Gantry angle ( IEC) 10 60 95 125 330 Beam energy (MV) 15 15 15 15 6 Dose/fx (MU) 65 47 58 201 184 Images in gate/fx 5.2 3.9 4.6 13.5 13.5 Total images in gate 78 58 69 202 201 Ave. visible seeds/image 2.2 2.3 2.0 2.6 1.3

treatment was planned to deliver 41.25 Gy to the target over 15 fractions. Treatment eld parameters are shown in table 1. Digitally reconstructed radiographs (DRRs) were created in the beams eye-view (BEV) for each eld. The eld edges and contoured seeds were superimposed on these images. 2.2. Patient set-up Breath coaching was continued throughout patient positioning and beam delivery each day. The patient position was set-up at end of exhale using simultaneous orthogonal diagnostic x-ray images captured with an onboard imaging system (Berbeco et al 2004b). The diagnostic imaging system has not yet been integrated with the RPM system, so manual gating was used. The set-up images were taken while the therapist was watching the RPM trace on a control room monitor. He/she took the images while the RPM signal was within the amplitude-gating window. We estimate that the error associated in the hand-eye coordination involved in this could be as large as the entire width of the gate, i.e. 5 mm. The threshold of action for moving the patient was also 5 mm when the set-up images were compared to the set-up DRRs. Future improvements to our set-up procedure, including integration with the RPM system, automated shift calculation and a smaller threshold of action should improve the accuracy of our gated set-up procedure. 2.3. Gated treatment Gated treatment was performed on a Varian 21EX linac (Varian Medical Systems, Palo Alto, CA, USA) equipped with an AS500 electronic portal imaging device (EPID) and the PortalVision software. A Varian real-time position management (RPM) system was used as an external surrogate-gating tool. During the treatment, the EPID was set to acquire images in the cine mode at a frame rate of approximately 1 image every 1.6 s. The integration time for each image was approximately 0.5 s. When in cine mode, EPID acquisition is not triggered by the linac. Rather, the EPID continuously, passively acquires images, even when the RPM signals the linac to hold off the therapy beam. No extra radiation is given to the patient. With this technique, many of the EPID images are taken during periods when the treatment beam is off. These blank images are discarded while the good images are kept (there is some ghosting, but it is trivial to determine which images are ghosts). In general, there is at least one good image from each beam-on period (RPM marker box is in the gating window), depending on the duration of the particular gate. For a treatment duty cycle of 30%, roughly

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(a)

(b)

Figure 1. (a) An in-treatment gated verication image acquired with the EPID. The three gold seeds are circled in yellow. (b) A DRR of the same eld, derived from the planning CT. The seed locations, GTV and PTV can be seen as contours.

1/3 of the acquired EPID images are analysable. The images were exported from PortalVision and analysed in a separate program. 2.4. Analysis An interactive data language (Research Systems, Inc., Boulder, CO, USA) program has been written to analyse the EPID images. Each image is examined ofine. The seed locations are digitized and compared to the corresponding seed contours in the DRRs. The eld aperture edges are used to register each treatment image with the corresponding DRR and the seed positions are quantied with respect to them. The seed positions in the treatment images are the result of both inter-fractional and intra-fractional variation. Due to the aforementioned issues with our diagnostic imaging set-up procedure, only the treatment images are used for analysis. The inter-fractional component is the patient positioning error. To assess the inter-fractional variation, the daily average of each seed position is calculated. The difference between the daily average of each seed and the corresponding seed contour was averaged over all ve elds for each day. This is the daily inter-fractional error. The treatment was coplanar so the superiorinferior coordinate is the only one used in this calculation. Whereas the interfractional analysis evaluates the accuracy of treatment, the intra-fractional analysis evaluates the precision of treatment. The intra-fractional component is the residual motion of the tumour within the gating window. This is calculated by nding the deviation of the seeds in each image from the daily average. Using the daily average as the reference point means that the set-up error (i.e. the inter-fractional error) is taken out of the intra-fractional calculation. Seed movement was seen prevalently in the SI direction during simulation; therefore we extracted intra-fractional information along this axis. 3. Results and discussion For the case study, a total of 608 analysable images were acquired over 15 fractions. The distribution of images per day and per eld is shown in table 1. An example of a good verication image is shown in gure 1(a) for eld #2. The corresponding DRR, with the GTV, PTV and seed positions contoured, is shown in gure 1(b). The seed positions over the entire treatment are shown in gure 2 for each eld. Also plotted is the DRR seed position for comparison. As an example, a close-up of the distribution for eld 4, seed #2 is shown

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Figure 2. The seed positions in the treatment images over the entire course of treatment are combined and shown for each eld. The position of each seed contour in the corresponding DRRs is represented by a crosshair (seed 1 = blue, seed 2 = green, seed 3 = red). The horizontal axis (x) is perpendicular to the SI, on the imager plane. The relation of x to the patient coordinates depends on the gantry position.

in gure 3(a). Note that this distribution is the combination of all images for the same eld, from all days. There are both inter-fractional and intra-fractional components leading to the spread in gure 3(a). These can be separated and investigated individually, as described in section 2.4. Figure 3(b) includes an overlay of the average seed position of each days treatment relative to the DRR seed position. The change of daily average (more easily seen in gure 3(c)) represents the inter-fractional variation.

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(a)

(b)

(c)

Figure 3. (a) A close-up of the locations of seed #2 in eld 4 over the entire course of treatment (black diamonds). The red crosshair is the location of the seed in the beams eye-view DRR. (b) Same as (a) but with blue diamonds representing the mean positions of the seed each day. (c) Only the daily mean positions are shown (blue diamonds), relative to the DRR seed position (red crosshair).

Figure 4. The inter-fractional variation for each eld, each fraction (i.e. 75 data points).

3.1. Inter-fractional variations The position of the daily average of each seeds position relative to the DRR is calculated. The inter-fractional variation in the SI direction for the combination of all the elds is shown in gure 4. The distribution has its mean at zero with a longer tail in the positive SI direction. To quantify the width of the distribution in gure 4, a 95% range was dened. This is the limit within which 95% of the data are located. For the sample patient, we found this to be +8.3/4.5 mm in the SI direction. The inter-fractional variation is plotted in gure 5 as a function of fraction for each eld individually and the average of all the elds. Our set-up images on day 6 showed the seeds to be just below the action threshold (5 mm), so no shift was made. On the same day, eld 3 (gantry at 95 ) was the only one in which a negative SI variation was found during treatment. This is due to the proximity of seeds 1 and 2 in the images at this angle (see gure 2). The analyst mistook the most superior seed for the one slightly more inferior. Days 8 and 9 had the

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Daily Interfractional SI Variation


10.0

Mean SI Variation (mm)

5.0

field 1 field 2 field 3 field 4 field 5 mean

0.0

-5.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Fraction
Figure 5. The daily inter-fractional SI variation is shown for each eld (see legend) and the average over all ve elds (red dotted line). Days 8 and 9 show variation greater than 5 mm.

Figure 6. The intra-fractional SI displacement for each of the 608 images.

largest variation, leading to the longer positive (superior) tail in gure 4. On day 8, the patient showed swelling in the stomach leading to a small rotation of the markers. Since rotation is not possible on our treatment couch, we made the best possible translation shift to accommodate the marker positions. It is unclear what led to the large variation on day 9. 3.2. Intra-fractional variations The distribution of SI motion for the combination of all of the elds is shown in gure 6. Note that the intra-fractional error for this patient in the SI direction is basically symmetric. The values for the 95% intra-fractional SI displacements are given in table 2. For the sample patient, we found the 95% ranges to be between 4.5 and 5.5 mm for the ve elds. The 95% range of the combination of all the elds is 4.8 mm. This is within 4% of the residual motion

3676 Table 2. The 95% range of residual motion over the entire course of treatment. Field 1 2 3 4 5 95% Range (mm) 5.5 4.5 4.5 5.3 4.4

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considered in the planning process (5 mm). This does not validate gating universally, but it does give us added condence in our gating procedure. 3.3. Seed visibility Not all seeds can be seen in every image. Some beam orientations produce better quality images due to the thickness of the patient in the beams eye-view and the relative positions of the clips and their proximity to high-density material (such as bone). The data in the last column of table 1 show that seeds could be better visualized from the 125 beam than from the 330 beam, even though the two are almost anti-parallel. The difference in beam energy may have also had an effect. The location of a seed can also be off by 1 mm because of its length. In the future, automated feature detection algorithms can be used to nd the seeds, relieving any inter-user variability. 4. Discussion of future work We have proposed a new technique for verication of respiratory-gated treatment, and demonstrated its feasibility in a case study. An EPID is used in the cine mode to acquire images of the patient during gated irradiation. The images can be compared to the planning DRRs for each eld to calculate the position of the tumour during irradiation. The data may be analysed retrospectively to assure accurate gated treatment. It may be benecial to develop faster analysis methods to enable assessment during the course of treatment (e.g. after each days session) or even online during the treatment. Online, real-time verication would require very fast recognition algorithms and integration with the EPID software. The technique presented here was shown to be useful for a case study in which tumour location could be deduced from implanted radiopaque markers. The implantation of markers may not always be feasible, however. There is evidence of a high risk of pneumothorax during percutaneous implantation of markers in the lung (Topal and Ediz 2003, Geraghty et al 2003, Arslan et al 2002, Laurent et al 2000a, 2000b). Some clinics have chosen an endoscopic method (Shirato et al 2003, Yamazaki 2004), however it has not been widely accepted. In the absence of radiopaque markers, the position of the tumour may be more difcult to nd. For some locations, the diaphragm may be in the eld of view and could act as a surrogate (Mageras et al 2001, Vedam et al 2003, Ford et al 2002, Dawson et al 2001, Wagman et al 2003, Kimura et al 2004, Plathow et al 2004a, Mageras et al 2004, Kim et al 2001, Onishi et al 2003, Plathow et al 2004b). For other locations, on the periphery of the lung, there may be enough contrast between tumour and lung to nd the tumour directly. Signicant image enhancing techniques may be needed to distinguish the tumour from the healthy anatomy (Berbeco et al 2004a). These and other techniques should be developed as alternatives to marker-based verication for the cases in which marker implantation is not feasible.

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With the effective tumour motion reduced by gating, clinicians may wish to prescribe an IMRT treatment. Obviously, the technique outlined here would have to be modied for that case. It has not yet been studied whether radiopaque markers can be seen in gated IMRT elds. If not, in-room or gantry mounted diagnostic x-rays may be needed to verify the marker position during irradiation. Drawbacks would be the elimination of the beams eye-view benet of the EPID and the delivery of some extra dose to the patient. 5. Conclusions We suggest the implementation of the technique outlined in this paper as part of gated treatment quality assurance. The quantities evaluated in this paper need not be the only information extracted from the data. Clinics may nd it useful to develop analyses to examine other relevant parameters. We will continue to use gating and build a statistical case for an appropriate clinical gating margin. A systematic study of a large sample of patients should be conducted to assess whether a single value for a motion margin should be used for all patients. The inter-fractional evaluation shows us that our set-up procedure may need some additional study and further data may suggest a suitable margin for patient set-up error. Acknowledgments This work was partially funded by grants from Varian Medical Systems, Inc. and the Whitaker Foundation. The authors would like to thank Dr John Wolfgang and Dr Greg Sharp for their help with this work. References
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