Index of content:
Volume 36, Issue 6, June 2009
- Industrial Physics Forum: Therapy Symposium: Ballroom D
- Locating and Targeting Moving Tumors
36(2009); http://dx.doi.org/10.1118/1.3182408View Description Hide Description
Accurate lungtumor tracking in real time is a crucial for image‐guidedradiotherapy of lungcancers. Existing lungtumor tracking approaches can be roughly grouped into three categories: (1) deriving tumor position from external surrogates; (2) tracking implanted fiducial markers fluoroscopically or electromagnetically; (3) fluoroscopically tracking lungtumor without implanted fiducial markers. The first approach suffers from insufficient accuracy, while the second may not be widely accepted due to the risk of pneumothorax. We have been developing various algorithms that facilitate the fluoroscopic lungtumor tracking without implanted fiducial markers. The talk will summarize what we have done and then discuss what we plan to do.
1. Understand the significance of and difficulty for real‐time localization of lungtumor
2. Understand various methods developed for markerless lungtumor tracking
Conflict of Interest: The research presented here is partially supported by Varian Medical Systems.
36(2009); http://dx.doi.org/10.1118/1.3182409View Description Hide Description
Recently, rapid development has been made in locating and targeting moving tumors. In practical treatment systems, latency induced by information acquisition, processing, communication and hardwarecontrol could significantly affect the targeting accuracy based on observed tumor locations. This talk focuses on introducing state‐of‐the‐art methods in target location prediction, and discussing the logical connections and differences among these methods. We will first make the principle distinction between the deterministic and stochastic perspectives.
For the deterministic setup, we will discuss the development in system representation, in terms of basis functions (such as Fourier and wavelet), and choice between parametric regression model (e.g., adaptive ARMA) and the nonparametric options, such as artificial neural networks and support vector machines. The less conventional stochastic perspective will be motivated by honoring a statistical interpretation of the familiar Kalman filter. Then a novel kernel density estimation based prediction approach will be introduced, which utilizes nonparametric probability learning techniques. Useful techniques such as state augmentation, and unified treatment for multi‐dimensional data will be covered. Some recent progress and unpublished results will be presented.
1. To systematically present the state‐of‐the‐art prediction algorithms
2. To discuss and analyze the connections among various developments
3. To address the practical considerations in selecting prediction methods for various types of target motions and system configurations.
36(2009); http://dx.doi.org/10.1118/1.3182410View Description Hide Description
DMLC tracking algorithms have emerged recently as a feasible solution of the delivery of intensity modulated radiation therapy in presence of motion of patient body anatomy. In this technique a MLC aperture, and beam dose rate, are dynamically adapted to trajectories of target and other organs in motion. There exist hierarchies of ever more sophisticated deliveries of this type that respond to increasingly realistic, and at the same time increasingly more complex, treatment conditions. The possibility of these various adaptations is rooted in multitude of leaf motions, and beam dose rate functions, that impose the same IMRT map over moving targets. Goals of tracking deliveries can evolve from finding solutions that are most time efficient to those that provide most benefit from dosimetric point of view.
The presentation will discuss cases of IMRTdelivery to rigid and deforming targets, will consider situations when target motions are known and reproducible at delivery as well as situations when these motions are irregular and unpredictable. The disadvantages of unintended variation in delivery to organs at risk will be discussed for solutions that deliver planned intensities to targets during tracking, while disregarding motions of organs at risk when differential motions between targets and organs at risk persist. The possibility of using additional degrees of freedom of mutual motion between organs at risk and targets for the benefit of the therapy will then be presented. The method of using beam dose rate variation for benefiting DMLC delivery will be explained.
1. Understand the origin of the DMLC IMRT tracking.
2. Understand the issues related to DMLC IMRT tracking in presence of complex motions of body anatomy.
3. Understand the issues related to therapeutic advantage rooted in motions of body tissues at radiation treatmentdelivery.
- Technical and Biological Innovations in Small Animal Image‐Guided Radiotherapy
36(2009); http://dx.doi.org/10.1118/1.3182320View Description Hide Description
Recent technical advances in small animal radiation devices allow laboratory irradiation of rodents under cone‐beam CT guidance with, in some cases, sub‐millimeter precision. This provides the opportunity for novel avenues of radiobiological research. Examples include radiation‐enhanced immunotherapy, normal tissue radiation response modeling, and localized radiation ablation of neural stem cell populations. Highlights from recent experiments will be reviewed and future proposed technical developments will be discussed.
36(2009); http://dx.doi.org/10.1118/1.3182321View Description Hide Description
An integrated, image‐guided irradiation system for small animal research has been developed. The system is capable of precise, accurate, reproducible and quantifiable 3D conformal delivery of radiationdose distributions to organs/tumors. The main hardware components are: (1) A Seifert Isovolt Titan 225 kV X‐ray tube with beam collimation provided by a custom‐made variable diameter “cone” or a set of motor‐driven symmetric “jaws”, thereby allowing field sizes from 0.5 mm in diameter to 7 cm square field at ∼33.5 cm SSD. (2) A six‐degrees‐of‐freedom (6DOF) robotic arm (Adept Viper s650) was integrated for precise animal positioning/motion (repeatability of ±0.020 mm in XYZ direction and angular precision of ±0.2°). The system is housed in a custom 6 × 6 × 6 ft3 shielded enclosure inside a laboratory. When the beam is aimed horizontally to (3) a flat panel amorphous silicon detector (XRD 0820 CN3, Perkin Elmer, Fremont, CA) a series of 2D‐radiographs can be recorded while the robot rotates the animal. Each image is composed of 1024 by 1024 pixels with a 200 μm pixel size at a frame rate of 7.5 Hz. An open source cone beam computed tomography(CBCT)reconstruction tool (OSCAR‐2, University of Toronto) using the Feldkamp‐Davis‐Kress (FDK) filtered back projection algorithm was implemented for CBCTimage reconstruction. Thus, targeting can be accomplished by the use of orthogonal radiographs and/or CBCT. A dose engine and CBCT‐based treatment planning are ongoing projects.
Dosimetric measurements and preliminary animal experiments have demonstrated the basic capabilities of the system in terms of radiationdose,dose rate and precision targeting. The system has also been used successfully in experiments to detect the molecular signaling occurring after spatially fractionated radiation therapy (GRID) in vivo.
A description of the system and a summary of experiments performed to date will be presented.
1. Appreciate the challenges of developing a high precision 3D conformal irradiator for small animals.
2. Learn about the main hardware components of the system and their integration.
3. Understand the advantages of using a 6DOF robot for imaging (motion) and beam delivery (positioning).
4. Learn about some of the potential research projects that such a system can make possible.
This research was sponsored by the Arkansas Biosciences Institute and the Central Arkansas Radiation Therapy Institute.
36(2009); http://dx.doi.org/10.1118/1.3182322View Description Hide Description
With the advent of advanced image‐guidance technologies, stereotactic body radiation therapy(SBRT), the application of an ablative dose of radiation given in one or few fractions and delivered with high accuracy, has emerged as a promising modality in the treatment of cancer. Despite this success, there is remains room in optimizing delivery and understanding response. In this regard, pre‐clinical studies can be very beneficial in systematically evaluating response and predicting and validating clinical protocols. We describe the development and application of a small animal irradiator, which provides high accuracy in target localization and radiationdelivery in a manner that mimics clinical SBRTdelivery. The essential characteristics of the irradiator include: a high dose rate (⩾ 10 Gy/min), allowing high dosedelivery in a clinically‐relevant time frame; precise target localization (⩽ 1 mm) to optimize irradiation to a tumor with respect to normal tissue sparing; and small radiation fields (1 to 10 mm) needed to implement the technology in small animals. The irradiator is based on a commercial X‐ray device (XRAD 320, Precision X‐ray, Inc.). The system can be operated at low energies (20–30 kVp) for high contrast imaging (essential for precise localization), and at high energies (⩾ 250 kVp) for therapeutic delivery.Radiation beam parameters, including energy specification (characterized by the half‐value layer — HVL), depth dose characteristics, and off‐axis profiles, have been determined through direct measurement. We describe the application of the device in a number of subcutaneous tumor, orthotopic tumor, and normal tissue models developed at our institution. Finally, the development of a next‐generation irradiator is also discussed.
TU‐C‐BRD‐05: Carbon Nanotube Field Emission Based Imaging and Irradiation Technology Development for Basic Cancer Research36(2009); http://dx.doi.org/10.1118/1.3182323View Description Hide Description
Caron nanotube(CNT)field emission is an emerging nanotechnology enabling the development of novel x‐ray imaging and radiation delivery systems for basic cancer research and clinical application. In this presentation a brief overview of the CNTnanotechnology and its recent development in the application of micro‐CT imaging, micro‐RT, cellular and tissue level microbeam irradiation will be presented.
The CNTfield emissiontechnology based systems have clear potential advantages over conventional imaging and irradiation systems based on thermionic emission. Micro‐RT and micro‐CT systems that are based on thermionic emissiontechnology commonly rely on a single radiation source and the imaging and irradiation depend on source rotation and thus can lead to poor temporal resolution for small animal research. The CNTfield emission based systems employ individually addressable multipixel cathode array radiation sources and thus are capable of high temporal resolution, static (no rotation) imaging and electronically shaping a small radiation field and its intensity map. In clinical application, a CNTfield emission based imaging and irradiation system can also improve treatment/imaging efficiency and improve patient throughput.
1. Understand basic principle of carbon nanotubefield emissiontechnology and its potential in imaging and irradiation technology development for cancer research and clinical application
2. Understand current status of the CNTfield emission based imaging and irradiation technology development
3. Understand the basic achievements and challenges in the technology development.
The research projects are supported grants from NIH R21 CA118351, U54‐CA119343‐01, R21CA128510, NC Biotechnology Center MRG‐1111, R33EB004204, and Xintek
Conflict of interest: Zhou is the Chairman of Xintek, Inc. and a board member of XinRay Systems, LLC
36(2009); http://dx.doi.org/10.1118/1.3182324View Description Hide Description
We will introduce small animalimage guided microirradiators by reviewing the concepts and requirements for high resolution and high conformality irradiation of tumors implanted in small animal limbs (xenograft tumor models), animalorgans and spontaneous tumor models. We will present two preclinical microirradiators developed by our group, a brachytherapy based microirradiator and an orthovoltage x‐ray source based microirradiator. The brachytherapy irradiator has been constructed around a commercial high‐dose rate (HDR) remote afterloader source in a teletherapy geometry. The system consists of a set of exchangeable tungstencollimators (from 2.5 to 5.5 mm diameter) mounted on an aluminum cylindrical support. An HDR catheter is then used to transport the source to the pre‐determined dwell position that centers the source at the collimator hole. With this microirradiator, the anatomical image is obtained using an external clinical CT operated at maximum resolution and coregistration is achieved using fiducial markers.
The x‐ray orthovoltage microirradiator has an onboard cone beam microCT subsystem for submillimeter low dose anatomical imaging. The microCT and the ontrovoltage x‐ray source are aligned using a common rotation axis in a tandem configuration. An axial motorized animal bed transfers the animal from the microCT subsystem to the microirradiation subsystem. The microCT subsystem was constructed using an 80 kVp micro‐focus x‐ray source with a 75 × 75 um2 focal spot and a flat panel amorphous silicon detector with 1024 × 1024 pixels. The orthovoltage irradiator subsystem was constructed using a 320 kVp x‐ray source with dual focus spots (0.4 × 0.4 mm2 at 800W and 1 × 1 mm2 at 1800 W). The orthovoltage beam is collimated using orthogonal jaws and exchangeable apertures. The treatment beam can be aimed at different latitudinal and longitudinal angles in steps of 2 arcmin. and translated at 100 μm steps (x, y and z). The beam cross sections can be modulated with submillimeter precision using steps of 50 μm. The system is designed to deliver a maximum dose rate of 40 Gy/ min.
These irradiators are operated under a common small animal irradiation facility that accepts campus wide preclinical projects. We will conclude our presentation by presenting examples of ongoing radiobiological projects that will allow us to illustrate the performance and operation of both irradiators.
36(2009); http://dx.doi.org/10.1118/1.3182325View Description Hide Description
Radiation therapy is a critical component in the management of cancer. However, our understanding of radiotherapy must continue to grow with improvements in conformality (e.g., IMRT) and as more targeted agents become available. Maximizing the therapeutic ratio will require a thorough understanding of biology of tumors and normal tissues. Small animalmodels of tumor response and normal tissue toxicity can provide unique insights into these issues, but have inherent limitations and challenges which must be overcome. As small animalimage‐guidedradiation therapy(IGRT) becomes feasible, one of the most important issues becomes “What questions do we want to ask?”. Pure radiotherapy questions such as dose, volume, and time/fractionation can be explored in appropriate small animaltumormodels while monitoring normal tissue effects. When combined with the ever‐increasing number of targeted agents, small animalIGRT becomes a powerful pre‐clinical tool that may allow optimal selection of agents and improve the timing and sequencing of concurrent therapies. After strong models of tumor control and normal tissue response are established, exploration of response biomarkers including novel imaging modalities becomes feasible. The wide‐spread availability of small animal multi‐modality imaging including CT, MR, optical, and US combined with novel contrast agents makes this an especially rich area of exploration. Some examples of previous small animalradiotherapy experiments with a brain tumormodel and ongoing exploration of normal tissues effects in lung will be reviewed and potential future studies attempting to link pre‐clinical and clinical data will be outlined.
At the end of this lecture, the audience will be able to:
1. Describe some of the challenges of small animalmodels.
2. Discuss the range of biologic experiments which may be feasible.
- The Physics and Challenges of Novel Proton Accelerators for Radiotherapy
36(2009); http://dx.doi.org/10.1118/1.3182206View Description Hide Description
We will review recent advances for ultra‐high gradient‐linac. We will show how the research on the basic phenomena of microwave breakdown in ultra‐high vacuum structure, led to novel geometrical designs that allow electron linac to achieve gradients in excess of 140 MV/m. Also, with the usage of copper alloys, one would hope to push this gradient to 180 MV/m. these advances can be applied to protonlinacs. We will present suggested designs for future protonlinacs, which would push the gradient to more than 70 MV/m. These will operate at high frequency in the X/Ku band. With this technology one hopes to design compact proton therapy machines at energies of ∼ 250 MeV, with fine control of energy. The compactness of the linac might allow the whole system to be installed on a single gantry.
36(2009); http://dx.doi.org/10.1118/1.3182207View Description Hide Description
A new type of compact induction accelerator is under development at the Lawrence Livermore National Laboratory that promises to increase the average accelerating gradient by at least an order of magnitude over that of existing induction machines. The machine is based on the use of high gradient vacuum insulators, advanced dielectric materials and switches and is being developed for a variety of applications. Research describing an extreme variant of this technology aimed at producing a compact, variable output linear accelerator for proton therapy for cancer will be described along with the technical challenges and issues. The goal of the development is to produce a proton accelerator that will fit in a standard linac vault and deliver intensity modulated proton therapy. Tomotherapy, Inc. has licensed the new accelerator technology from the Lawrence Livermore National Laboratory and the Compact Particle Acceleration Corporation (CPAC) is supporting development of the system. Research sponsored by Tomotherapy, Inc. and CPAC.
Conflict of Interest: Some of the co‐authors have a financial interest in Tomotherapy, Inc. and/or CPAC.
36(2009); http://dx.doi.org/10.1118/1.3182208View Description Hide Description
Purpose: Significant efforts have been made through federal, industrial and institutional funding to develop cost‐effective alternatives to conventional accelerator‐based particle therapy. This presentation reviews the development of laser‐accelerated particle beams as an alternative to conventional accelerators for particle therapy. Method and Materials: Many institutions and research groups have focused on their research on the applications of laser‐accelerated proton and ion beams for medical applications, in particular for radiotherapy treatments. These include extensive investigations of optimal laser parameters and target designs to achieve therapeutic particle energies, compact particle selection and beamcollimationdesigns for novel compact particle therapy systems, dose calculation and treatment optimization for laser‐accelerated protonbeams, and system and shielding designs for clinical prototype machines. Fox Chase Cancer Center has established a laser‐ion acceleration facility that consists of a commercial 150 TW laser, custom‐made laser‐pulse compression and target chambers, particle selection and beam collimating devices, dosimetry monitoring systems and shielding constructions. Initial laser‐proton acceleration experiments were performed with thin aluminum and plastic foils as target materials. Particle‐in‐cell (PIC) simulations were carried out to investigate the optimal laser parameters and target configurations to facilitate laser‐proton acceleration and dosimetric studies. Results: The maximum proton energy achieved by laser acceleration was 58 MeV. Our initial testing with a 1018 W/cm2 laser intensity (at 20 TW) produced up to 4 MeV protons with a broad energy spectrum, which confirmed the scalability of laser intensity and maximum proton energy. A compact shielding designed was investigated using Monte Carlo simulations that allows for the installation of the particle therapy head on a small rotating gantry. Conclusion: Laser‐accelerated proton and ion beams have a great potential to replace conventional radiotherapy systems due to its compact design and cost‐effectiveness. Many technical and engineering issues must be solved before a clinical prototype can be built for radiotherapy applications.
36(2009); http://dx.doi.org/10.1118/1.3182209View Description Hide Description
Protonradiotherapy for cancer is growing in the US and around the world. This growth is due to the physical advantages of the improved ability to deposit most of the radiationdose in the tumor, as opposed to x‐rays where most of the dose is deposited in normal tissues. In the US there are currently five proton therapy centers treating patients and over 2,300 x‐ray based linear accelerator facilities. Limiting the widespread application of protonradiotherapy to the general cancer patient community is the capital, building and operating costs associated with protonradiotherapy that exceed $ 100 million per site, a substantial cost differential with x‐ray based facilities. A compelling approach is to combine the physical advantages of proton therapy into a smaller, cheaper, gantry mountable system that can be widely disseminated. This requires a radical breakthrough in accelerator technology, however, as the size and mass of such an accelerator would have to be at least an order of magnitude less than those of conventional cyclotrons and synchrotrons. The Plasma Physics Laboratory at Stanford has developed a novel particle accelerator that is based on a newly‐understood second mode of operation in co‐axial plasma accelerators. By processing a plasma instead of a pure ion gas, the proposed accelerator is fundamentally different from electrostatic accelerators, resulting in two important advantages. First, a plasma gas contains electrons and positive ions, making it macroscopically neutral. As a result, it can tolerate high ion densities in a very compact device. Second, a plasma can conduct very high currents and self‐induce strong magnetic fields. This can be used to accelerate the plasma electromagnetically via the Lorentz force. The particle energy then becomes a function of the current to mass flow ratio rather than of the applied voltage. Eliminating the need for applying high voltages enables the generation of bursts of extremely energetic particles from a comparatively simple and inexpensive device. The recent identification and stabilization of a second mode of operation in coaxial plasma accelerators makes the advantages of plasma‐based approaches accessible to protonradiotherapy. The distinct features of the proposed plasma‐based accelerator may also result in attractive advantages when compared to alternative compact accelerator concepts that are currently under development.
This lecture will provide an overview of the differences between plasma and pure ion acceleration, as well as some of the limitations that have historically limited plasma accelerators to low beam energy applications. It will then summarize the advantages of operating in the second mode and describe the challenges that have to be overcome to scale and develop the existing proof of concept prototype into a viable therapy machine.
36(2009); http://dx.doi.org/10.1118/1.3182210View Description Hide Description
The centre for proton therapy at the Paul Scherrer Institute was expanded recently following the commissioning of a new superconducting‐magnet cyclotron (COMET) dedicated to patient treatment. The accelerator was built by ACCEL Instruments GmbH (Varian), based on a design from the National Superconducting Cyclotron Laboratory (Michigan State University). The cyclotron is specified to provide a 500 nano‐Ampere beam of protons at a fixed energy of 250 MeV. The large magnetic field (∼ 3T) required at extraction is provided by the superconducting coils. A high power radio‐frequency system, operating at 72.8 MHz (second harmonic of the cyclotron frequency) provides the required acceleration of protons following their emission from a cold‐cathode ion source. The facility has also been up‐graded with the addition of new gantry (Gantry‐2) for patient treatment and a new beam line dedicated to eye treatments (OPTIS2). A novel feature of COMET is the high beam extraction efficiency (> 80%). This limits component irradiation and facilitates the regular maintenance periods which are an important consideration for any patient treatment center where high reliability and availability are required. We will describe the modes of operation of PROSCAN and, in particular, the spot‐scanning technique used to irradiate tumours. Magnetic elements permit rapid transverse deflection of a pencil beam for two dimensional scanning. An energy “degrader” allows rapid scanning in energy over the range of 70 – 238 MeV. This results in a variable depth of penetration of the beam, thus permitting a complete three dimensional scan. The beamlines which transport protons from COMET towards the two patient gantries and to OPTIS2 will also be discussed. They require sophisticated diagnostics for safe and reliable use of the facility. The various diagnostics include ionization chambers, secondary emission monitors and multi‐leaf Faraday cups. They are used to measure beam current, profile, position, halo and loss. The role of the diagnostics as interlocks for safe operation of the beamlines will also be described.
1. Understanding the principle of the spot scanning technique.
2. Understanding the issues concerning diagnostics for safe beam‐line operation.