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91 Seiten, Note: 1,0
2 Related Work and Patents
3 Managing Respiratory Motion in Radiation Therapy
3.2 Treatment Planning
3.3 Motion-encompassing methods
3.3.1 Slow CT scanning
3.3.2 Inhalation and exhalation breath-hold CT
3.3.3 Four-dimensional CT/respiration-correlated CT
3.4 Respiratory Gating Methods and Procedures
3.4.1 Internal Gating
3.4.2 External Gating
3.5 Clinical Procedure
4 Image Sequence Synchronization
4.2 Proposed Method
4.3 Similarity Matrix
4.4.1 Gain Removal
4.4.2 Wild Card
4.4.3 Transition matrix
4.5 Model-based Dynamic Programming
5 Clinical Prototype
5.2 Clinical Systems
5.2.1 SOMATOM Sensation Open
5.2.2 ONCOR Linear Accelerator
5.2.3 Respiratory Gating System
5.3 Clinical Applications
6.2 Level I: Synthetic Data
6.3 Level II: Phantom Data
7 Discussion and Future Work
7.2 Wild Card Detection Improvement
7.3 Model Improvement
7.4 Cone Beam Acquisition Integration
7.5 On-the-fly Expansion
7.6 Registration Improvement
List of Figures
List of Tables
Auf dem Gebiet der Bestrahlungstherapie gab es in den letzten Jahren weitreichende Entwick- lungen und Fortschritte. Eine besondere Bedeutung auf diesem Gebiet ist der Bestrahlung von Tumoren im Brust- und Bauchbereich zuzuschreiben. In diesen Regionen werden sowohl die Positionen von Organen als auch von Tumorgewebe innerhalb des Körpers signifikant durch die Atmung des zu behandelnden Patienten beeinflusst. Die daraus resultierende Bewegung des Tumorgewebes wird durch eine Erweiterung der zu bestrahlenden Fläche kompensiert. Diese Erweiterung beinhaltet alle möglichen Positionen des Tumors und erstreckt sich somit auch auf gesundes Gewebe
Mehrere klinische Studien belegen eine höhere Erfolgsquote bei erhöhter Strahlendosis. Um möglichst wenig gesundes Gewebe einer solch hohen Strahlung auszusetzen verwenden Ärtze das Konzept der ’gated radiotherapy’. Derzeit gängige Ansätze basieren auf der Überprüfung eines Ersatzsignales. Dies kann sowohl ein implantierter Marker, als auch ein externes Signal sein, welches versucht die Atmung des Patienten zu erfassen
Innerhalb dieser Arbeit werden Grundlagen und Methoden von ’gated radiotherapy’ erläutert. Zusätzlich wird eine Übersicht über aktuelle Patente und Produkte auf diesem Gebiet gegeben, sowie Vor- und Nachteile derzeit gängiger Ansätze diskutiert
Basierend auf dieser Diskussion wird eine neu entwickelten Methode vorgestellt. Diese vereint die Vorteile beider bereits bekannten Ansätze, vermeidet dabei jedoch deren Nachteile. Der hierfür entwickelte Algorithmus bedient sich bildbasierter Verfahren und Methoden der medizinischen Bildverarbeitung. Er berechnet eine Zuordnung zwischen einem 4D - CT Plan- nungsvolumen und einer kurz vor der Behandlung aufgenommenen Röntgenbildsequenz des- selben Patienten. Mit Hilfe dieser Zuordnung ist es dem Arzt möglich auf Basis eines exter- nen Atemsignals Grenzen für die Bestrahlung zu definieren und den Patienten nur in speziellen Phasen der Atmung zu bestrahlen
Der entwickelte Algorithmus ist in einen bereits existierenden medizinischen Prototypen integriert, entwickelt von Siemens Corporate Research (SCR) in Princeton, NJ, USA. Mit Hilfe dieses Prototyps wird die Anwendbarkeit der Methode demonstriert. Zudem ist ein weiterer Prototyp zur Aufnahme von Röntgenbildsequenzen, synchronisiert mit einem Atemsignal, entwickelt worden. Beide Applikationen werden innerhalb dieser Arbeit vorgestellt
Far reaching developments and technical advances took place within the field of radiotherapy in the last years. Radiotherapy within the chest and abdomen area is especially important in the field of radiotherapy. Within this regions, organ and tumor positions are significantly affected by patient respiration. The tumor motion, caused due to respiration is compensated by extending the treated area. This extension covers all possible positions of the tumor and therefore also includes healthy tissue Several clinical studies provide evidence of a survival advantage for higher dose levels. To spare a maximum of healthy tissue physicians use ’gated radiotherapy’. Common recent ap- proaches for gated radiotherapy are based on the observation of a surrogate. This either can be an implanted fiducial marker or an external signal, which is trying to capture the patients’ respiration
Within this thesis principles and methods of ’gated radiotherapy’ are described. Additionally an overview of recent patents and products related to radiotherapy are presented and advantages and disadvantages of both common approaches are discussed. This discussion leads to a new developed method, which is introduced. The method joins advantages of both known methods but disregards their disadvantages. The developed algorithm is using image guided methods and methods of medical image processing. A mapping between a 4D-CT planning volume and a most recent acquired fluoroscopic sequence of the same patient is calculated before treatment. Using this mapping and an external breathing signal the physician can define gating intervals and treat the patient in certain breathing phases
The developed algorithm is included in an existing prototype developed by Siemens Corporate Research (SCR) in Princeton, NJ, USA. Using this prototype, the application of the method is shown. Furthermore another prototype to acquire respiration synchronized fluoroscopic sequences is developed. Both applications are introduced within this thesis
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Lung cancer is still the most fatal type of cancer, even though the cases of death have been declined in the last years. Regarding to the American Cancer Society (ACS), lung cancer was the reason for almost 29% of all cancer deaths in the United States in 2005. There were 172,570 new estimated cases diagnosted with an estimated 163,510 deaths. Although one can recognize a continuous downward movement of deaths caused by lung cancer in the past 16 years, it is important to improve early detection and treatment continously (Figure 1.1).
Besides radiation therapy lung cancer is also treated with surgery, chemotherapy, and targeted biological therapies, depending on the type and stage of the cancer. Regarding to the ACS, the 1- year relative survival rate for lung cancer was 42% in 2000, however the 5-year relative survival rate for all stages combined was only 15% [Ame05].
Receiving radiation treatment therapy especially in the thorax and abdomen area causes a major health risk for patients. As the tumor is moving due to intrafraction organ motion which is mainly caused by patient respiration, physicians have to treat healthy tissue as well. Facing this movement, physicians are inevitable stuck in their decision about a proper treatment for the patient. On the one hand to be able to deliver x-rays throughout the whole treatment physicians have to increase the treated region by the whole range, where the tumor potentially could be. On the other hand there is clinical evidence of survival advantage for higher dose levels [Oku95], [Per86] [Mac05]. Concerning these two conflictive issues, physicians are biased. Increasing the dose level would accord a better chance of survival, but regarding the extended treatment region, a lot of healthy tissue would be exposed to this high dose, too. Certainly, this is very bad for the patient.
An optimal designed system should provide the radiation oncologist both opportunities. The oncologist still should be able to use a higher dose for treatment, but at the same time minimal
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Figure 1.1: Age-Adjusted Cancer Death Rates, US, 1930 - 2002; Source: US Mortality Public Use Data Tapes 1960 - 2002, US mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2004 healthy tissue should be harmed. Therefore a system should both consider patient respiration and enable a significant decrease of the treated area.
About 15 years ago, physicians came up with the idea of using gated radiotherapy to face this problem [Oha89]. The general idea of gated radiotherapy is to reduce the incidence and severity of normal tissue complications and to increase local control through dose escalation. In order to obtain these issues, a range of values within the treatment beam is turned on has to be specified. Therefore the localization of the tumor has to be known first. This either can be achieved by tracking an implanted fiducial marker or by assuming a correlation between an external surrogate placed on the patient chest for example. Hence, gated radiotherapy is divided into two groups (Figure 1.2):
- internal gating
- external gating
Both methods are based on the observation of a surrogate, where the correlation between an internal surrogate is considered to be more accurate than a correlation between an external surrogate and the real tumor position. Considering these two methods, there are various problems and each method has its own advantages and disadvantages, respectively (Table 1).
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Figure 1.2:: Internal Gating, a fiducial marker is implanted in the tumor (green) and used as a surrogate;: External Gating, an external surrogate is used, assuming a correlation between the tumor and the surrogate
Internal gating requires additional dose for the patient because image acquisition is necessary to locate the implanted marker properly. This additional dose can be more than what is clinically acceptable for patients with many treatment fractions or a long treatment time of a single fraction. Furthermore internal gating is difficult for thoracic tumors or even not possible because fiducial markers cannot be inserted and there is a risk of pneumothorax.
In opposite external gating is non-invasive but it is quite inaccurate because there often is a bad correlation between the external surrogate and the real tumor position. Consolidating, current state of the art techniques are not satisfying enough in a clinical environment.
With this thesis a solution using image guided methods is provided. This solution joins the advantages of internal and external gating and abandons the disadvantages of both techniques (Table 1). The proposed algorithm is computing an image-based mapping immediately before treatment which is based upon a reference breathing cycle and the current breathing of the pa- tient. During the treatment the breathing pattern is observed by an external surrogate which can be compared to the computed mapping. Therefore no surgery is required and the patient is only exposed to a short additional dose which is just used to acquire a few breathing cycles. Further- more the correlation is computed prior the treatment and is not based upon external surrogates, but on patient images where breathing phases and tumor position are known.
To obtain this goal, a general overview of literature related to this topic as well as related
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Table 1.1: Comparison of internal / external gating and 4D Image Verification
patents are presented first. Afterwards basic principles of gated radiotherapy and there fields of application are described. As the therapy is divided into a planning and a treatment stage, the requirements for a planning setup are shown. Furthermore motion-encompassing methods to ac- count tumor motion are discussed and introduced. Based on acquired data using these methods it is possible to apply internal and external gating techniques. Examples for both of them are also presented within this theses. Finally an example for a clinical treatment procedure and guide- lines for gated radiotherapy are introduced. Accordingly the proposed image guided method is discussed in detail and all necessary technical background is introduced. As the developed al- gorithm has to be tested in clinical environment, its implementation into an existing prototype is also described within this theses. Additionally a second prototype to acquire fluoroscopic sequences correlated with a breathing signal is introduced. Medical devices used for data acqui- sition are also introduced, as well as a use case for the application of the prototype. To appraise the quality and ability of the proposed solution various results of performed tests are discussed and proposals for further developments are presented in the end.
Many studies related to respiratory motion and gated radiotherapy for lung cancer have been published in literature. Since gated radiotherapy is a recent technology, there are still a lot feasibility and evaluation studies being performed. This chapter provides an overview of published work within the last years and points at the latest products in the 4-D treatment market which are introduced in detail in the following chapter. Recently, the American Association of Physicists in Medicine (AAPM) has released a report about the management of respiratory motion in radiation oncology [AAP06]. As this report is a recommendation on how to manage respiratory motion, it is a valuable source for background informations about the topic dealt within this theses and therefore taken strongly into consideration within the next chapter.
Applying gated radiotherapy to lung tumors requires some understanding about tumor motion in general. Various evaluations about this issue have been published lately, e.g. [Pla04], [Err03], [Six03], [For03], [Man03], [Sep02], [Ste01], [Shi01], [Gir01], [Ekb98]. Summarizing these studies, the motion magnitude can be clinically significant and depending on tumor sites and individual patients. The range is within the limits of a few centimeters.
Once it is obvious how tumor motion is behaving it is essential to figure out if and how tumor motion is correlated with a respiratory signal. [Mag04], [Ahn04], [Hoi04], [Tsu04], [Koc04], [Ved03] provide an overview of this correlation (Table 2).
Furthermore, it is proven that there is a clinical evidence of survival advantage for higher dose levels [Oku95], [Per86] [Mac05]. To deliver such a highly conformal radiation dose distribution to a complex static target volume physicians can use intensity-modulated radiation therapy in combination with gated radiotherapy (gated IMRT) [Kub00].
Once it is obvious that there is a correlation between breathing and tumor movement, the theoretical background for gated radiotherapy is given [Oha89], [Ort95] (see chapter 3.1). Com-
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Table 2.1: Correlation of tumor/organ motion with the respiratory signal; 3D: three - dimensional, AP: anterior - posterior, CT: computed tomography, MRI: magnetic resonance imaging, pts: patients, s: second(s), SI: superior - inferior [AAP06]
mon terms for tumor volumes are discussed in two reports of the International Commission on Radiation Units and Measurements [ICR93], [ICR99] (see chapter 3.1).
Keall performed a theoretical analysis of margins to examine potential reduction of CTVPTV margins, which is the main goal of gated radiotherapy [Kea02]. A second study regarding the reduction of CTV-PTV margins confirms a possible reduction of the margin, using gated radiotherapy [Bar01] (see chapter 3.1).
These margins are created and defined in a process called treatment planning. Sean provides principles and guidelines for lung cancer treatment planning [Sen04a], [Sen04b] (see chapter 3.2). The reference sequence used within the treatment planning phase is acquired by using motion encompassing methods (see chapter 3.3). Three of these methods are introduced within this thesis. These methods are slow CT scanning [Lag01] [Kos01], inhale and exhale breath-hold CT [Bal98], [Aru98] and 4D-CT/respiration-correlated CT [Son05] [Lu05] [Pan04] [Rie05].
As mentioned before gated radiotherapy can be divided into two sections, internal gating and external gating. As an example for an internal gating system, the real-time tumor-tracking radio- therapy (RTRT) system developed jointly by Mitsubishi Electronics and the Hokkaido University is introduced [Kun99] [Shi01] [Shi00c] [Shi00a] [Shi03] [Shi99] [Kit02] [Shi00b] (see chapter 3.4.1). Currently another internal gating system is developed by Calypso Medical Technologies which avoids some disadvantages of the RTRT system [Kra02]. External gating systems are provided by Varian Medical Systems [For02] [Mos02], BrainLab [Sch01] and Siemens Medical Solutions (see chapter 3.4.2).
To understand the clinical process of gated radiotherapy an example developed at the Massachusetts General Hospital (MGH) and guidelines from the American Association of Physicists in Medicine (AAPM) are introduced [Jia05] [AAP06] (see chapter 3.5).
The proposed algorithm is embedded into an existing project developed by Siemens Corpo- rate Research [Kha06]. This project comprehends required algorithms for patient positioning and similarity measurements like mutual information [Wel96]. To obtain a solution for the given problem the core algorithm uses Dynamic Programming [Bel57], [Dre77] which is modified by a model-based approach. The underlying model is based upon the principles of markov chains [Mar71]. However, to achieve valuable input data for the core algorithm, some preprocessing steps have to be applied. Within the preprocessing step an existing significant gain field has to be removed, which is done by taking advantage of the singular value decomposition (SVD) [Tre97]. General explanation of markov chains and dynamic programming are based upon [Nie83].
Since Wilhelm Conrad Roentgen discovered X-rays in 1895, overwhelming possibilities in cancer treatment were potentiated. Within the last century and especially recent years this powerful technology was continuously improved [Ort95]. Nowadays radiation oncologists are able to relieve pain or even cure cancer by using Roentgens X-rays. However, even after more than 100 years of research there are still problems in delivering X-rays in a way the therapy has the highest probability of cure with the least morbidity at the same time.
One of these problems is respiratory motion of tumor targets. Due to breathing, tumor sites located in the thorax and abdomen are especially affected by respiratory motion. Especially one kind of cancer is extremely difficult to treat, which is lung cancer. The position of tumors located in the patient’s lung is especially affected by respiration during treatment sessions. As respiration is regulated in the medulla by stimulating the diaphragm, this is an ’involuntary’ action the patient cannot prevent, even though breath hold techniques could control breathing in a restricted way.
To facilitate the gas (O2 - CO2) exchange between blood and air, the diaphragm is contin- uously being contracted and relaxed. This mechanism has a quite significant impact on organs and tumors. General speaking referring to respiratory motion literature, one cannot assume a general respiration pattern for particular patients prior to observation and treatment. Breathing patterns are individual and dissimilar for each patient. Concerning a specific patient, breathing patterns vary not only from one treatment session to another but also even during a single session as well [Sep02] [Nei06]. Motion between two sessions is called inter-fraction motion whereas the motion during a treatment session is called intra-fraction motion.
Farther in terms of tumor volumes, there are four terms to address certain tumor and treatment regions in literature [ICR93], [ICR99]:
- Gross Tumor Volume (GTV): is referred to as the tumor itself
- Clinical Target Volume (CTV): GTV extended by the areas of sub-clinical disease
- Planning Target Volume (PTV): internal margin considering the organ movement and possible setup errors are added to the GTV
- Internal Target Volume (ITV): internal target volume incorporating the motion of GTV
As the gross tumor volume is not covering all possible afflicted tissue, the physicians have to extend the volume to cover metastasis and other sub-clinical disease. In order to treat moving tumor targets, all locations of a possible residence of the tumor have be covered as well. However as already stated before, creating and irradiating a PTV leads to a suboptimal solution because a lot of healthy tissue is constantly exposed to high doses. In order to avoid this problem and to improve radiation treatment, physicians can apply respiratory gated radiation therapy.
In the late 1980s and early 1990s respiratory gated radiation therapy was developed in Japan first [Oha89]. The technique relies upon a correlation between tumor motion and respiration, using a respiration signal as a surrogate. Irradiation is only performed in a specific state of the breathing cycle, as the tumor is roughly at the same location of the body each time the patient is in a specific breathing cycle state. While the tumor is moving within this specified part of the breathing cycle, it is moving within the so called ’gate’ or ’gating window’ (Figure 3.1). According to this term the name of gated radiotherapy is derived.
There are two different types of gating:
- Displacement Gating:
In order to apply displacement gating, the relative position between two extremes of breathing motion, namely, inhalation and exhalation is measured. The beam is activated whenever the respiration signal is within a range of relative positions.
- Phase Gating
Breathing is divided into breathing phases, like begin of inhale, maximum inhale or end of exhale. Often these phases are also referred to percentage levels, like 10% inhale or 10% exhale. Whenever the patient’s respiration is within certain phases, the beam is turned on.
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Figure 3.1: Application of a gating window; the tumor (blue) is moving [a], the corresponding breathing curve is shown in [b], and the gating window (beam on) is indicated by the red border
In an idealized gated treatment, tumor position should be directly detected and the delivery of radiation is only allowed when the tumor is at the right position. However the direct detection of the tumor mass in real-time during the treatment often is difficult or even impossible. Therefore a system needs to know the patients’ respiration to verify the predefined gate as well as to observe surrogates, which can either be an external respiration signal or an internal fiducial marker.
Apparently, the duration of a treatment session is extended if gated radiation therapy is ap- plied because the beam is not able to deliver X-rays continuously. But this leads to the primary objective of gated radiation therapy. Treating the tumor just at specific positions opens a poten- tial for a significant decrease of the CTV-PTV margin and therefore tumors can be treated with higher dose levels. These levels are measured in gray units (Gy), which is the absorption of one joule of radiation energy by one kilogram. At the moment, studies on the clinical or dosimetric gain of margin reduction are rare and preliminary. Theoretical analysis of margin reduction by studying phantoms using gated radiotherapy promise a reduction of 2-11 mm in the CTV to PTV margin [Kea02]. Another study showed, that using deep inspiration breath hold techniques on average decreases the percent of lung volume receiving > 20Gy (V201 ) from 12.8% by 11% without and by 8.8% with CTV-PTV margin reduction [Bar01]. According to this, gated radiotherapy enables the possiblity of exposing less healthy tissue to high dose levels and therefore the patient has a chance to achieve a better long-term survival rate.
As mentioned before, treatment sessions are obviously consuming more time, because tu- mors are irradiated just within certain breathing phases. The ratio of beam-on time to the total treatment time is referred to as duty cycle and is a measurement of the treatment efficiency. As some tumor motion still occurs within the gate, this motion is also called residual motion. How- ever, there is always a trade-off between duty cycle and residual motion, because increasing the duty cycle results in a larger residual motion of the tumor. Usually both phases are taken into consideration during the treatment planning. According to physicians there is usually a larger duty cycle achieved during exhale than during inhale. Therefore most patients are treated at full exhale if there is a larger duty cycle required. For a more accurate gating and a stable residual motion patients are gated at full inhale, because this breathing phase is more reproducible than full exhale.
In the following, an overview of principles and methods to account for respiratory motion in radiotherapy is given. This section is abutted to the AAPM Task Group 76 report ’The Management of Respiratory Motion in Radiation Oncology’ [AAP06].
The main objective of defining a CTV-PTV margin is founded in possible geometric and setup errors. Therefore, a planning session is scheduled before the patient is treated. Within this session an acquisition of the target region using one of the below described methods is done. This acquisition is used by physicians to define the CTV-PTV margin. Principles and guidelines for treatment planning regarding lung cancer can be found in two publications by Senan et al. [Sen04a], [Sen04b]. The following components take influence on CTV-PTV margins definitions for lung cancer:
- Inter- and intra-observer variations in GTV delineation:
Due to different experience and education of physicians, target regions are defined different quite often [Gir02]. Therefore a defined GTV region is dependent on the physician and not unique.
- Motion artifacts in the CT scan (during planning):
As patient breathing and cardiac activity is present during the acquisition of a planning CT scan these two components could case artifacts. These artifacts lead to systematic errors during treatment, because the defined region is based upon this acquisition.
- Respiratory motion and heartbeat (during delivery):
As in the CT scan, respiration and heartbeat also occurs during treatment and cases tumor motion [Sep02].
- Daily variations of respiratory motion:
Due to the fact that the planning sequence is usually acquired several days / weeks prior to the treatment daily variations of respiratory motion have a quite significant effect on tumor position and movement [Sep02] [Nei06].
- Treatment-related anatomic changes including tumor size
As the goal of radiation therapy is a shrinkage of the tumor during treatment this changes are also effecting the design of the regions and have to be taken into consideration for long-term treatment processes.
- patient setup error
Because the region is defined by using a prior acquisition the patient has to be positioned exact at the same position for the treatment. Possible positioning errors should also taken into consideration while planning the regions [Ekb98] [Err03].
As mentioned before, the CTV-PTV margins are usually designed based upon one of the following motion-encompassing methods, which are slow CT scans, breath-hold CT or 4D-CT scans.
As it is important to estimate the mean position and range of motion during CT imaging, because respiration induces tumor motion during treatment several techniques are existing to account this problem. The introduced techniques are dealt in the order of the increasing workload.
The first method is called slow CT scanning and provides an opportunity to acquire multiple respiration phases per slice [Lag01] [Kos01] [Kos03]. Therefore, the CT scanner is operated very slowly, and/or multiple CT scans are averaged. As most CT scanners are able to acquire a slow CT scan this application can be implemented at almost every location, which is a big advantage of this method. Images which are acquired by using this method are showing the full extent of respiratory motion that occurred during the acquisition. Therefore, the couch has to stay at the same position for the whole acquisition time. The loss of resolution due to motion blurring is one disadvantage of slow CT scanning. Another disadvantage is the increased dose for slow CT compared to conventional CT scanning.
Other wide available methods to obtain tumor-encompassing volumes are inhale, exhale and breath-hold CT scans [Bal98], [Aru98]. These scans can also be acquired at most clinics today. Physicians only have to concern about the ability of a patient to tolerate more than twice the scanning time, because both an inhale and an exhale scan has to be acquired. Patients receiving this type of acquisitions have to be able to hold their breath reproducibly. After acquiring these two scans, a maximum intensity projection (MIP) tool can be used to obtain the tumor-motion- encompassing volume. The main advantage of this method compared to slow CT scanning is the reduced blurring during the acquisition.
The most recent technology is called 4D - CT or respiration - correlated CT [Son05] [Lu05] [Pan04] [Rie05]. Using this method, the mean tumor position and range can be determined for treatment planning. Figure 3.2 shows a schematic of 4D - CT using a cine acquisition process. The CT couch is moving during the acquisition and multiple slices are acquired for each couch position. Therefore, each couch position delivers several time synchronized images showing different breathing phases. After sorting these images, the complete 4D - CT sequence consists of multiple 3D-CT datasets, where each datasets represents a single breathing phase. However, there are also limitations for this method. If respiratory patterns vary during the acquisition of the 4D-CT, artifacts can be observed. A typically 4D-CT sequence covers 8 to 25 phases. Using this technology, inhale, exhale as well as slow CT scans can be reconstructed. It is also possible to apply a MIP tool, to obtain the tumor-motion-encompassing target volume.
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Figure 3.2: A schematic of the 4-D CT process using cine acquisition. At each couch position images for many respiratory phases are acquired (images of the same respiratory phase are indicated by colors). Afterwards, the time synchronized images are sorted and put together to multiple 3D-CT volumes, which make up a 4D-CT sequence together.
Before an overview of existing respiratory gating methods is given a basic tool in gated radio- therapy is introduced first, which is Digital Reconstructed Radiography (DRR). Using DRRs it is possible to locate tumor positions and as the name says DRR are digital reconstructed images. The technique is very similar to ray casting, where virtual beams are sent through a 3D (CT) volume. These beams are projected on a 2D plane, where each pixel sums up the intensities of the beam intersecting the pixel. This tool is used for many of the following methods.
There are two different approaches for internal gating introduced in this thesis. The first intro- duced technology is the realtime tumor tracking radiotherapy (RTRT) system, developed jointly by Mitsubishi Electronics, Co., Ltd, Tokyo and the Hokkaido University (see Figure 3.3) [Kun99] [Shi01] [Shi00c] [Shi00a] [Shi03] [Shi99] [Kit02] [Shi00b]. It is based on radiographic detec- tion of implanted fiducial markers, which can be tracked at video frame rate [Shi00c]. Therefore, a 2 mm diameter gold sphere fiducial markers is implanted near or even in the tumor and can be tracked three dimensional by using a pair of stereotactic kilovoltage X-ray imaging systems. Thus the linear accelerator is delivering radiation, if the tumor position matches for both camera
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Figure 3.3: The motion-gated linear accelerator system and fluoroscopic real-time tumor tracking system. Three of the four fluoroscopic systems are shown [Shi00b].
systems and is within the planning range. As the selection of patients has to be considered very well within this approach, maximum benefit for the patient has to be ensured, before applying this invasive procedure. It is mandatory for the patient to be able to remain motionless on the treatment couch for up to 45 min during a treatment sessions. Patients also have to agree with the implantation process. However, there are several problems with patients having lung cancer, because pulmonary function criteria have to be determined before implanting the markers and the risk of pneumothorax is also present. As described before, ahead the treatment session there usually is a treatment simulation or planning session set, where CT scans are acquired. DRRs generated based upon these scans are replicated with the images acquired in the treatment room and used to locate the implanted fiducial markers. In advance of each treatment, the patient is repositioned regarding the monitored fiducial path for several breathing cycles. Each imaging system has to detect a coincidence of the gates to enable the beam. Therefore treatment times are usually longer than 30 minutes. Summarizing the major strength of this system, there is a pre- cise and real-time localization of the tumor position during the treatment. The implanted internal markers are often valid as good surrogates for tumor positions. However, there are also two major weaknesses of this technology. Implantation of markers in the lung cause a risk of pneumothorax and there also is a high imaging dose required for fluoroscopic tracking. Currently, this system is the only internal gating system used in clinical environment today.
However there is a second system in development and not yet released, which is a non- ionizing system by Calypso Medical Technologies, Inc. The system promises not to require additional high imaging dose as the just introduced system. As it is also an internal gating
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Figure 3.4: The Varian RPM system: [a] shows the placement of the external fiducial marker which is observed by the CCD video camera system; [b] shows the breathing curve including the beam on / off signals; source: www.varian.com
system it is tracking the tumor by localizing implanted electromagnetic markers. These markers are implanted in or near the treatment site and can be registered to the patient’s treatment target prior to treatment [Kra02].
Regarding external gating, a first feasibility study with a Varian 2100C accelerator, as well as an evaluation of different external surrogates signals were made at the University of California at Davis [Kub96]. Later in a joint venture with Varian Medical Systems a gated radiotherapy system using a video camera to track inferred reflective markers on a patients’ abdomen was developed [For02]. This system was commercialized later by Varian and is one of the most widely discussed external respiration systems today [Mos02]. Another similar system is developed by BrainLab, this system is also able to determine the internal anatomy position using X-ray imaging during treatment [Sch01]. Furthermore, Siemens Medical Systems offers a gating interface with its linear accelerator using an Anzai belt system. The linear accelerator as well as the Anzai belt system are introduced later in this thesis. All of the just mentioned systems are FDA-approved and can be used in therapy.
As all these products rely on an external surrogate and no intervention is needed, this method can be applied to almost all patients. However breathing training is needed to improve the likelihood of the patient completing the simulation session.
Usually an external gating system like the Varian Real-time Position Management (RPM) system is observing an external fiducial marker (Figure 3.4). Related to the RPM system, this marker is an infrared reflective plastic box placed on the patient’s anterior abdominal surface to maximize the AP respiratory-induced motion. This surrogate is monitored by a charge-coupled- device (CCD) video camera mounted on the treatment room wall. The system allows both dis- placement and phase gating. To secure the treatment the system is using a periodicity filter. This filter checks the regularity of the breathing waveform and disables the beam immediately when the breathing waveform becomes irregular. Such an irregular breathing waveform occurs if the patient is coughing or moving. The beam is enabled again after establishing regular breathing again.
The Task Group 76 of the American Association of Physicists in Medicine recommend for patients in whom respiratory motion may be a concern to apply a decision process as shown in Figure 3.5 [AAP06].
As topic two in Figure 3.5 shows, the Task Group recommends that either a greater than 5 mm range of motion in any direction or significant normal tissue sparing should be a criterion to apply respiratory managed techniques. To provide an overview of how a clinical process is proceeded, a treatment procedure developed at the Massachusetts General Hospital (MGH) is introduced. This procedure describes an image guided respiration gated (IGRG) treatment procedure for gated liver and lung radiotherapy [Jia05]. It suggests seven steps and uses the Varian RPM system for patient respiration monitoring and gating and additionally an Integrated Radiology Information System (IRIS) for image guidance. As the usage of only an external surrogates is quite uncertain, the MGH recommends to use 4D - CT scanning, gated radiographic setup and cine EPID (Electronic Portal Imaging Device) as well as patient breath coaching together with the RPM system. Furthermore, the procedure requires implanted fiducial markers for liver tumors and clear anatomic features near the target for lung cancer. As mentioned before, the procedure includes seven major steps:
1. Patient selection and preparation:
There are several issues to be considered before a patient is selected to receive gated ra- diotherapy. The MGH procedure determines suitable patients within three steps. Since a breathe coaching technique is used during treatment, it is important that patients are will- ing and able to follow such instructions. For liver tumor treatment sessions, the patient should already have radio-opaque markers implanted inside or near the tumor and for lung tumors clear anatomic features near the tumor. The last criteria is the range of intra-fraction motion. To gain most advantages in using gated radiotherapy, this range should be quite large.
2. Breath training and motion assessment:
Due to breathing control, physicians are able to control the patient’s breathing and therefore are furthermore able to reproduce breathing patterns throughout the whole treatment course. Therefore, a breath training session of one hour is scheduled on the simulator, where fluoroscopic images are taken and a initial gating window is determined.
3. 4D-CT simulation:
Before the treatment a 4D-CT simulation is scheduled, where both a free breathing and a coached helical 10 phase CT scan is acquired. Using this scans, the physicians specify a gating window, considering the balance between residual motion and duty cycle.
4. Treatment planning:
Physicians contour in each of the ten 4D-CT datasets GTV and/or CTV. These contours are used to define a composite target volume, that includes the residual motion. As the end of exhale phase is used as planning CT, the composite target volume is fused to the 4D - CT data set within this phase. Critical structures are contoured on the end of exhale CT data set and a margin is added to CTV to obtain the PTV. Additionally, a backup plan with a larger margin for non-gated treatment is also created using the free breath CT scan.
5. Image guided patient setup:
As in conventional treatment the patient is initially set up using laser alignment to skin tattoos. Furthermore, the RPM system is applied to the patient to be able to monitor and coach the patient’s breathing. A pair of gated AP and lateral IRIS radiographs are taken at the end of exhale phase after the patient is properly coached. These gated radiographs are matched with DRRs to detect patient shifts.
6. Gated treatment delivery:
After the patient is positioned, the patient is treated under breathe control using the RPM system. Additionally, EPID images are taken in cine mode during the delivery of each field. These images are used for treatment verification within the next step.
7. Treatment verification and assessment:
Within the last step, the recorded EPID images are analyzed retrospectively. To verify the gated treatment, the residual marker motion in the gating window is measured. Therefore, the treatment can be modified by reducing the gate, if the residual motion is significantly larger than what was estimated during the simulation [Ber05].
Looking at this procedure, a brief overview of the clinical use-case of gated radiotherapy is given. Basically, gated radiotherapy is divided into three major phases. First there is the planning phase, where a 4D-CT scan is acquired and margins for the gate are set. Depending on the type of gated radiotherapy this phase also can occur a few weeks before the second phase, which is qualified as the treatment phase. Within this phase, the patient receives treatment based on the planning phase. In the last phase, applied treatment plans are verified and adjusted for further treatment sessions.
illustration not visible in this excerpt
Figure 3.5: Recommended clinical process for patients with whom respiratory motion during the radiotherapy process is a concern [AAP06]
1 the volume of lung treated to a dose of = 20Gy
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