Real-time tumor tracking using implanted positron emission markers: Concept and simulation study Tong Xu,a Jerry T. Wong, Polad M. Shikhaliev, and Justin L. Ducote Department of Radiological Sciences University of California, Irvine, California 92697 Muthana S. Al-Ghazi Department of Radiation Oncology, University of California, Irvine, California 92697 Sabee Molloi Department of Radiological Sciences, University of California, Irvine, California 92697 Received 4 January 2006 revised 14 April 2006 accepted for publication 27 April 2006 published 26 June 2006 The delivery accuracy of radiation therapy for pulmonary and abdominal tumors suffers from tumor motion due to respiration. Respiratory gating should be applied to avoid the use of a large target volume margin that results in a substantial dose to the surrounding normal tissue. Precise respira- tory gating requires the exact spatial position of the tumor to be determined in real time during treatment. Usually, fiducial markers are implanted inside or next to the tumor to provide both accurate patient setup and real-time tumor tracking. However, current tumor tracking systems require either substantial x-ray exposure to the patient or large fiducial markers that limit the value of their application for pulmonary tumors. We propose a real-time tumor tracking system using implanted positron emission markers PeTrack . Each marker will be labeled with low activity positron emitting isotopes, such as 124 I, 74 As, or 84 Rb. These isotopes have half-lives comparable to the duration of radiation therapy from a few days to a few weeks . The size of the proposed PeTrack marker will be 0.5���0.8 mm, which is approximately one-half the size of markers currently employed in other techniques. By detecting annihilation gammas using position-sensitive detectors, multiple positron emission markers can be tracked in real time. A multimarker localization algo- rithm was developed using an Expectation-Maximization clustering technique. A Monte Carlo simulation model was developed for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq PeTrack marker was determined to be 0.7���5.0 Gy at 10 mm from the marker. At the center of the field of view FOV , the sensitivity of the PeTrack system was 240���320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The sensitivity was reduced by 45% when the marker was near the edge of the FOV. The scatter fraction ranged from 12% 124I, 74As to 16% 84Rb . In addition, four markers labeled with 124I inside a 30 cm diameter water phantom were simulated to evaluate the feasibility of the multimarker localization algorithm. Localization was considered successful if a marker was localized to within 2 mm from its true location. The success rate of marker localization was found to depend on the number of annihilation events used and the error in the initial estimate of the marker position. By detecting 250 positron annihilation events from 4 markers average of 62 events per marker , the marker success rates for initial errors of ��5, ��10, and ��15 mm were 99.9%, 99.6%, and 92.4%, respectively. Moreover, the average localization error was 0.55 ��0.27 mm, which was independent of initial error. The computing time for localizing four markers was less than 20 ms Pentium 4, 2.8 GHz processor, 512 MB memory . In conclusion, preliminary results demonstrate that the PeTrack technique can potentially provide real-time tumor tracking with low doses associated with the marker���s activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk. �� 2006 American Association of Physicists in Medicine. DOI: 10.1118/1.2207213 Key words: radiation therapy, organ motion, real-time tracking I. INTRODUCTION Radiation therapy remains one of the principal modalities for localized treatment of malignant disease. Recently, there have been significant improvements in radiation therapy de- livery techniques. Multileaf collimator based intensity modu- lated radiation therapy IMRT ,1 tomotherapy,2 intensity modulated arc therapy IMAT ,3 and robot-based radiosurgery4 have become available. As compared to con- ventional three dimensional 3D conformal therapy 3DCRT , these techniques can significantly improve dose conformity to the planning target volume. Advances in anatomical and functional imaging modalities CT, MRI, SPECT, PET, and US have led to improved visualization and delineation of 2598 2598 Med. Phys. 33 ���7���, July 2006 0094-2405/2006/33���7���/2598/12/$23.00 �� 2006 Am. Assoc. Phys. Med.

tumors.5 Despite these encouraging advancements, tumor motion due to respiration remains a limiting factor in the delivery accuracy of radiation therapy for pulmonary and abdominal tumors.6 Studies have shown that upper- abdominal tumors can move as much as 30 mm during respiration.7,8 Respiratory gated radiation therapy should be applied to optimize the target volume margin and minimize the dose to surrounding normal tissues. Precise respiratory gating requires determining the exact spatial position of the tumor in real time during treatment. Skin marker and spirometer-based techniques provide indirect indications of tumor position, which can introduce significant tracking errors.9,10 Even when the external respiratory surrogates are well correlated with the implanted x-ray fiducial markers prior to each treatment fraction, the residual motion can still be large due to the intrafractional variation of the patient���s breathing pattern.10���12 Real-time tumor tracking can provide accurate respiratory gating or even tumor-tracked radiation therapy. A real-time tumor tracking technique using 1.5���2.0 mm gold markers monitored by two x-ray fluoroscopy systems has been previ- ously reported.13 However, this technique requires x-ray fluoroscopy throughout the radiation therapy session. The skin dose resulting from x-ray fluoroscopy during real-time tumor tracking can exceed 1 Gy per hour of treatment time.14 The fluoroscopy dose is a concern if fluoroscopy based tumor tracking is synchronized with tomotherapy, robot-based radiosurgery, or IMRT, using a multileaf collimator.14 An electronic portal imaging device EPID based tumor tracking technique15 is limited by low image contrast and the possibility that the marker may be outside the radiation field segment. Seiler et al. have proposed a magnetic sensor based technique.16 However, it requires wires to be connected from outside the patient���s body to the implanted sensors. Another reported technique localizes the tumor using implanted wireless electromagnetic transponders.17 The transponder���s large size 1.8 8 mm makes its application in the lung difficult because of the high incidence of pneumothorax 35% with 1.3 mm diameter biopsy needle .18 Sajo et al. have proposed a technique to locate brachy- therapy seeds with positron emission tomography PET by labeling the seed with a positron emission isotope.19 How- ever, their technique was not designed for real-time tumor tracking, and a conventional PET system can only provide a localization accuracy of approximately 4���5 mm. Bemrose et al. suggested a method for tracking a single particle labeled with a positron emission source for engineering applications such as flow measurement.20,21 This technique can provide real-time tracking of a single particle with submillimeter pre- cision. We propose to apply this principle to real-time tumor tracking using implanted positron emission markers. We call this tumor tracking technique ���PeTrack.��� The PeTrack tech- nique uses radio-opaque markers filled with a low activity 1���10 MBq positron emission source. The positions of the markers can then be determined by detecting pairs of anni- hilation gammas from the positron source using two pairs of position sensitive gamma detectors mounted on the linear accelerator gantry. The proposed technique can provide real-time tumor tracking with low dose to normal tissue. This technique will increase the feasibility of precise respiratory gated IMRT, tumor tracked radiation therapy,22,23 and robotic motion com- pensated radiosurgery.4 The implantation of positron emis- sion markers with diameters of 0.8 mm or smaller will be easier than the implantation of existing markers. II. CONCEPTUAL DESIGN OF THE PETRACK SYSTEM A. Overall system design The PeTrack system uses positron emission markers and position sensitive gamma ray detectors to localize the tumor position in real time. The radio-opaque markers labeled with a short half-life positron emission source can be implanted inside or around the tumor. Two pairs of position sensitive gamma ray detector modules can be installed on the linear accelerator linac gantry at 50���70 cm from the isocenter. Figure 1 shows the arrangement of detectors around the linac, where detectors A1 and B1 are attached to the sides of the Linac head and detectors A2 and B2 are mounted on the linac gantry through an adjustable arm. The dimensions of the detector modules are estimated to be 20 20 30 cm3. The angle between the two detector pairs can vary from 65�� to 90��, depending on the dimensions of the linac head. The detector modules can rotate around the patient with the gan- try. By acquiring positron annihilation events from each marker, the positions of the markers can be determined in FIG. 1. A depiction of the four PeTrack detector modules A1, A2, B1, and B2 mounted on the linear accelerator gantry 50 cm from the isocenter. 2599 Xu et al.: Real-time tumor tracking using implanted positron emission markers 2599 Medical Physics, Vol. 33, No. 7, July 2006