Tumors in the thorax and abdomen move up to several centimeters during respiration. This intra-fraction motion impacts all forms of external beam radiation therapy and is an issue that is becoming increasingly important in the era of image-guided radiotherapy. This article presents the concepts and methods of a recently developed approach that is a type of real-time respiratory motion tracking.

Calvin R. Maurer, Jr., Ph.D. is the VP of research at Accuray Inc. He has led the research and development of several technologies at Accuray including image fusion, Monte Carlo dose calculation, treatment plan optimization, image-based tracking, and beam collimation using internal research efforts and collaborations with external partners. Dr. Maurer can be reached at 408-716-4600 or

Figure 1: The key subsystems of the CyberKnife Robotic Radiosurgery System shown in this figure are the robotic manipulator; the compact linear accelerator; the x-ray imaging system; the stereo camera system, which is part of the Synchrony Respiratory Tracking System; and the treatment table.
Several approaches have been developed to manage the dosimetric effect of respiratory motion in radiation therapy delivery. One straightforward approach is to enlarge the clinical target volume (CTV) to a planning target volume (PTV), within which the target should move during the breathing cycle. The variation in target position associated with breathing can be determined by examining the range of target motion with fluoroscopy, slow CT scanning, or a 4D CT image study. Although compensating for respiratory motion by increasing target volume margins can ensure that tumor motion during breathing will not affect the dose delivered to the target, it increases the dose delivered to normal tissues, which can be a particular problem when the lesion is located close to organs at risk.

Another set of approaches attempt to minimize the margin by delivering radiation when the tumor is at a relatively fixed and reproducible position. Breath holding has long been used in diagnostic radiology to reduce the blurring of images. For radiation therapy, the goal is to attain the same breath-hold position between beams delivered during treatment fractions. Treatment is delivered during the breath-hold period. Breath holding is physically demanding and uncomfortable, and breath-hold repeatability and patient compliance are challenges, especially for elderly patients or patients with compromised pulmonary capacity, common among patients with lung cancer or other pulmonary disease. Thus, breath-hold methods may not be applicable to a significant population of patients.

With respiratory gating approaches, the patient continues breathing normally. The radiation beam is turned on only within a specified portion of the patient's breathing cycle, which is commonly referred to as the "gate." The position and width of the gate are determined by monitoring the patient's respiratory motion using an external respiration signal. The delivery of radiation during a limited portion of the breathing cycle can substantially reduce the duty cycle (the ratio of the gate width to the respiratory cycle period) and thus, increase the treatment time. The duty cycle is typically about 25%. Lesion motion and gating model stability, which can adversely impact the planned dose distribution, are also challenges for gating methods.

Respiratory Motion Tracking

Figure 2: Illustration of direct tumor tracking. The image registration process involves a block matching search in which the matching window (blue square in the top image) containing the tumor region (blue contour inside blue square) from the DRR (top image) is moved throughout a user-defined search window (white square) in the treatment x-ray image (middle image) to find the region in the x-ray image most similar to the matching window from the DRR (blue square in middle image). The matching window is the minimal encompassing rectangle that contains the entire tumor. The bottom image shows the value of the image similarity measure, which is pattern intensity, for all searched blocks in the search window. The block in the x-ray image most similar (highest value of the similarity measure) to the matching window corresponds to the tumor location (blue square in middle image). All other blocks in the x-ray image (black squares) have smaller similarity values.
Another way to manage respiratory motion is to dynamically move or shape the radiation beam to follow the tumor's changing position, an approach that is often referred to as real-time tracking. Continuous real-time tracking can substantially reduce the size of the tumor-motion margin added to the CTV while maintaining a 100% duty cycle for efficient dose delivery.

Real-time tracking requires a method to move or shape the radiation beam relative to the moving target. For photon beams, there are three main ways to achieve this: move the patient using the treatment couch, change the aperture of the collimator, and move the beam by physically repositioning the radiation source [e.g., linear accelerator (LINAC)]. Robotic couch-based motion tracking has been shown to be technically feasible for real-time compensation of intra-fraction respiratory motion. However, continuous couch motion associated with real-time respiratory motion tracking has the practical issues of patient comfort and treatment tolerance. Alternatively, the beam can be effectively moved by changing the aperture of the collimator. The technical feasibility of this approach has been demonstrated for a multi-leaf collimator (MLC). However, there are several potential technical limitations to this approach. For example, the MLC motion required for target tracking superimposes on that required for intensity modulation, increasing the chances of exceeding the physical speed limitations of the MLC. A third approach is to physically reposition the radiation source to follow the tumor's changing position. The Synchrony Respiratory Tracking System is a realization of this approach.

Synchrony Respiratory Tracking System
The CyberKnife Robotic Radiosurgery System (Figure 1) moves the radiation beam by physically repositioning the radiation source. A miniature lightweight 6 MV X-band LINAC is mounted to an industrial multi-jointed robotic manipulator that can move freely and accurately aim the radiation beam with six degrees of freedom. Two digital x-ray imaging systems are orthogonally configured. The x-ray generators and amorphous silicon x-ray detectors are rigidly fixed so that their projection camera geometry is calibrated and known with high accuracy. Computer algorithms automatically compare the projection images of the target region with the patient's treatment planning CT image.

The Synchrony Respiratory Tracking System is an integrated subsystem of the CyberKnife system that allows irradiation of extracranial tumors that move due to respiration. One advantage is that patients can breathe normally during continuous treatment, enabling no reduction in the duty cycle.

Figure 3: External optical markers used by the Synchrony system to provide a breathing signal.
The primary concept in the Synchrony system is a correlation model between internal tumor position and external marker position. In order to reduce radiographic imaging exposure, episodic radiographic imaging is combined with continuous measurement of an external breathing signal. At the start of treatment, the internal tumor position is determined at multiple discrete time points by acquiring orthogonal x-ray images and performing image registration. Synthetic x-ray images, commonly referred to as digitally reconstructed radiographs (DRRs), are generated from the treatment planning CT image by casting rays through the CT image using the known x-ray imaging system geometry to simulate the x-ray image formation process. The tumor position can be determined by aligning the positions of implanted fiducial markers in the DRRs with the marker locations in the x-ray images. Alternatively, direct tumor tracking can be performed by image registration of the tumor region in the DRRs to the corresponding region in the treatment x-ray images (Figure 2). A linear or quadratic correlation model is then generated by fitting the 3D internal tumor positions at different phases of the breathing cycle to the simultaneous external marker positions. An important feature of this method is its ability to fit different models to the inhalation and exhalation breathing phases. During treatment, the internal tumor position is estimated from the external marker positions using the correlation model and this information is used to move the linear accelerator dynamically with the target. The model is checked and updated regularly during treatment by acquiring additional x-ray images.

The Synchrony system uses external optical markers to provide a breathing signal. Three optical markers are attached to a snugly fitting vest the patient wears during treatment (Figure 3). The optical marker positions correspond to the chest wall position. Light-emitting diodes (LEDs) transmit light through optical fibers that terminate at the cylindrical optical marker. The optical markers are sequentially strobed and a stereo camera system, consisting of three linear charge-coupled device detector arrays, measures the 3D marker positions continuously at a frequency of approximately 30 Hz.

Figure 4: Schematic block diagram of the Synchrony Respiratory Tracking System. For each external marker, there is a correlation model between the position of the internal target (XT) and the position of the external markers (XM). The outputs of the individual models are averaged to obtain the present time estimate of the target position. A predictor is used to compensate for communication latencies and robotic manipulator inertia. Finally, the predicted position is filtered and sent to the robotic manipulator as a positioning command.
A schematic block diagram of respiratory motion tracking in the Synchrony system is shown in Figure 4. There is a separate correlation model for each external marker. The external marker positions are measured continuously and input to the corresponding correlation models. Each model provides an estimate of the target position from the external marker variable. The individual estimates are averaged to get the final estimate of the target position. This value represents the position of the target at the present time. Ideally, this value can be sent to the robotic manipulator as a position command without any delay. However, communication latencies along with robotic manipulator and LINAC inertia cause delays; if the present time estimate of the target position is sent to the robot, there will be a lag in the robot manipulator's motion. A predictor compensates for the delays in the system using the history of the target movement. It is adaptive and is designed to respond quickly to changes in the breathing pattern and target movement. Finally, the output of the motion predictor is passed through a smoothing filter before it is sent to the robot as a position command.

Inter- and intra-fraction changes in position and motion are common. A correlation model that addresses the issue of inter-fraction variability is generated at the beginning of every treatment. However, the target position and motion typically changes during the treatment. This could be caused by gradual patient relaxation throughout the treatment period. In the lung, this could be attributed to gravity action on compliant lung tissue. Thus, it is important to regularly check and update the correlation model during treatment. This is accomplished in the Synchrony System by acquiring additional x-ray images every one to two minutes. Each newly acquired data point is used to update the correlation model and thus, the model adapts to gradual changes in target position and motion during treatment.

Patients are living, breathing beings, and this movement must be taken into account if ultimate treatment accuracy is to be achieved. The CyberKnife System with the integrated Synchrony Respiratory Tracking System offers real-time tracking for tumors that move with respiration. Patients lie comfortably and breathe freely as the treatment beam is moved in "synchrony" with respiration, allowing highly conformal delivery of radiation to tumors with the smallest possible margins.

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