X-RAD SmART (Small Animal RadioTherapy) IMAGE GUIDED BIOLOGICAL IRRADIATOR Technical Specifications (updated March 2015)

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1 X-RAD SmART (Small Animal RadioTherapy) IMAGE GUIDED BIOLOGICAL IRRADIATOR Technical Specifications (updated March 2015) The X-RAD SmART Small Animal IGRT research system provides a high accuracy cone beam CT imaging system and a high dose delivery therapeutic X-ray source into a single platform. Although fully functional, it is designed to allow future development to be integrated without significant redesign. This self-shielded system consists of the following items: 1. Shielded Cabinet: X-RAD SmART IGRT Cabinet Cabinet walls removed for interior display only The X-RAD SmART cabinet is available in 3 different sizes to accommodate a wide variety of laboratory spaces. The standard cabinet fits in most laboratory settings and will do a fine job with a plethora of experiments. The smaller X-RAD SmART Mini is designed for laboratories where space is at an absolute premium, and can accommodate any experiments with mice and rats. The larger X-RAD SmART Plus can accommodate larger laboratory animals, such as the largest New Zealand white rabbits, small canine specimens and micropigs. 1

2 Cabinet Dimensions: I. X-RAD SmART: 76.5 h x 60 w x 41 d (196cm h x 154cm w x 103cm d) II. X-RAD SmART Mini: 76.5 h x 43 w x 41 d (196cm h x 110cm w x 103cm d) III. X-RAD SmART Plus: 76.5 h x 66 w x 41 d (196cm h x 170cm w x 103cm d) Cabinet Weight: I. X-RAD SmART: 1950kg (4290 lbs) II. X-RAD SmART Mini: 1700kg (3740 lbs) III. X-RAD SmART Plus: 2300 kg (5060 lbs) Large specimen loading door provides easy access inside chamber Rotational Cable Management System allows seamless operation Roof Mounted Ventilation Port to allow for gas anesthetic venting Fully Shielded side port for anesthesia tubing and vitals monitoring systems Externally controlled LED-based interior lighting X-RAYS ON Warning Light on roof of cabinet Cabinet meets safety requirements of US Federal Regulation 21 CFR Shielding Details Shielded for 225 kv with exterior leakage less than 1 μsv/hr at 10 cm (<0.5mR/hr in USA) Leaded glass window (4 cm) thick Walls constructed of Steel/Lead/Steel (shown below) 2

3 1.2. Radiation Interlock Details Physical Interlock on door: Door must be closed for electrical circuit to complete from generator to x-ray tube. X-rays cannot activate with door open. Shown below: Emergency Stop Switches: A total of 4 Switches: 1 inside cabinet, 1 on light switch panel, 1 on x- ray console, and 1 on the wall outside of cabinet Motion control stop switch on inside of door: Prevents gantry rotation and stage movement while cabinet door is open. 2. X-Ray Unit: The X-ray unit is comprised of a power supply, X-ray tube and cooling unit. PXI employs industrial, non-destructive testing (100% duty cycle) grade equipment in order to provide long term reliability and improved performance. The X-ray power supply is positioned outside the radiation enclosure for ease of routine maintenance and positioning flexibility X-Ray Power Supply Manufacturer: GE (Germany) Model: ISOVOLT Technical Data: Maximum Output Voltage: 225kV Maximum Output Current: 45 ma (limited to 30 ma for selected X-ray tube) Maximum Output Power: 4.5 kw (limited to 3 kw for selected X-ray tube) Control & Display Accuracy: 0.1kV, 0.01mA Absolute Accuracy: ±1% Certification: CE declaration of conformity Dimensions: 350 x 870 x 850 mm (W x D x H) Weight: 189 kg Electrical: 1N PE 230V ±5%, 50/60Hz, 10 KVA or 3N PE 400/230 ±10%, 50/60Hz, 8KVA 3

4 Other Features: Automatic Warm-up time selection ISOVOLT TITAN E Controller included Remote operation via PC control 2.2. X-ray Tube Manufacturer: Comet (Switzerland) Model: MXR225/22 or MXR225/ Technical Data: Unipolar Metal Ceramic Tube Nominal Operating Voltage: 225 kv Continuous Rating: 640W / 3000 W (4500W for MXR 225/26) Focal Spots: IEC336: d=.4 mm / d=3.0 mm EN12543: d=1.0 mm / d=5.5 mm Target Material: Tungsten Inherent Filtration: 0.8mm Be Cooling Medium: Water Note: An optional 640W / 4500 W X-ray tube (Comet MXR 225/26) is now available with all other specifications above remaining the same Cooling Unit Manufacturer: GE Model: WL3000SE Technical Data: Dimensions: 479 x 398 x 481 mm (L x W x H) Weight: 38kg empty Coolant: Water Coolant Capacity: 3.7 liters Noise Level: 55 db (A) at 1 meter distance Power: 230 VAC, 2.5A (supplied by X-ray Power supply) Other Features: Can be located up to 20 meters from cabinet, in a separate industrial room 4

5 3. Collimation and Filtration System The Collimator/Filter Mount is permanently attached to the X-Ray tube and precisely aligned to center the position of the beam precisely at the treatment isocenter. It is a modular configuration that allows for interchanging of filters and collimators to suit specific experiments Collimator/Filter Mount Assembly Collimator Block The Collimator block provides fixed beam collimation to expose a field slightly larger than the 20 x 20 cm imaging area of the detector panel. The size of the field at isocenter is just greater than 10 x 10 cm, owing to a system magnification factor of Filter Slide Insert Beam hardening filters are inserted into the path of the x-ray beam to deliver the appropriate spectrum for each application. Typically, a softer 2.0 mm Al filter is employed for imaging tasks ( kvp), while a harder 0.3 mm Cu filter is employed for treatments at 225kVp. These are defined in more detail in section Ionization Chamber Integration There is an option for a built-in mounting system for an optional PTW 7862 Parallel Plate Ionization Chamber that will allow measurement of reference dose prior to delivery to the specimen. This measures dose as it exits the x-ray tube, and can be used as a quantitative reference to measure beam stability Collimator Mounting System Collimators are inserted into a mounting system and precisely held in position by a spring loaded door assembly Beam Conditioning Filters The Beam Conditioning Filters are configured from Aluminum, Tin and Copper to provide various half-value layer compositions as required by the users. Currently, (2) beam filters are defined for use, however a wide variety of filter combinations are available Imaging Filter #1 Currently, Imaging is performed at lower kv energy ( kvp) which requires the following filter: F1 = 2mm Al (HVL = 2.8mm Al at 100 kvp) Treatment Filter #2 Currently, Treatment is performed at higher kv energy (225 kvp) which requires the following filter: F2 = 0.3mm Cu (HVL = 0.9 mm Cu at 225 kvp) Custom Filtration solutions are available upon request 5

6 3.3. Collimators Fixed collimators are precision manufactured devices that contain a primary collimator and secondary trimmer to significantly sharpen beam penumbrae. Cones are manufactured from brass and use lead inserts for beam definition. All cones are designed to collimate at 30 cm SAD (source to axis distance), and will provide a clearance of 7cm CID (cone to isocenter distance) on all sides. Although any size can be manufactured from 0.5mm diameter to 10cm x 10cm, the following sizes (at isocenter) are currently available. Circular: 0.5, 1, 2.5, 3.5, 5, 8, 10, 15, 20, 25 mm Square: 3x3, 5x5, 10x10, 15x15, 20x20 mm Rectangular: 8x12, 10x20, 10x30, 30x40 mm An adaptable Field Shaping Collimator is also available. The user can change the field size by cutting the desired field in a blank lead or tungsten sheet. Any field shape up to a 10x10cm square can be created. If a user has a desired collimator in mind, but not the expertise to manufacture it, PXI are capable of designing and manufacturing customs collimators to the user s specifications. The custom field can also be integrated into SmART Plan. All drawings are made available for user development and modification Adjustable Field Collimator (2015) Design of an adjustable field collimator to perform dynamic and intensity modulated therapies has been in the works for some time. The collimator will feature adjustable octagonal field sizes from 1 to 40 mm, and will be fully integrated into both Pilot and SmART Plan. The design and commissioning is currently at the refinement stage, and this will be available in Q

7 4. Animal Stage and Rotational Gantry The X-ray tube and Image Detection Panel rotate slightly more than 360 degrees in order to generate a full CT image set and provide coplanar treatments at any angle. The Animal Stage provides precise motion in all Cartesian directions for precise and accurate targeting. All motions are driven by high quality stepper motors and controlled via a motion controller in software Rotational Gantry The Rotational Axis (Gantry) axially supports the X-ray tube, imaging panel & shutter assembly. At one end, a motorized center hub allows cables to exit the cabinet while maintaining full radiation shielding. The other end of the gantry is supported by a large precision ring that provides geometric stability, but also provides a method to support additional equipment that may be added or developed in the future. IG Targeting Precision (unambiguous targets) is better than 0.1 mm. Listed are some of the gantry s characteristics: Supports X-ray tube, Imaging Panel, Shutter and Bioluminescent Imaging Camera Very smooth o rotation Rotation Speed: Adjustable 0.01 to 3 RPM Positioning Accuracy: better than 6 arc minute resolution Rotational limit and home detection proximity switches Provides a 30 cm source to axis distance (SAD) Additional shielding is permanently mounted behind imaging panel 4.2. Animal Stage The animal Stage provides precision X-Y-Z motion of the specimen table using stepper motor driven linear stages controlled by the Pilot software. The animal platform attaches to the vertical stage via a quick-release fastener that allows animal exchange to be performed rapidly. Listed are some of the stage s characteristics: High precision X-Y-Z motion with relative position encoders on all axis Load Capacity: 125lbs (56 kg) Positional accuracy: 35 μm, Repeatability: ± 20 um Positioning Velocity, Adjustable: Up to 36mm/sec Standard Stage Size: o X-RAD SmART 3 x 12 x 1/8 in. o X-RAD SmART Mini 3 x 6 x 1/8 in. o X-RAD SmART PLUS 3 x 12 x 1/8 in. Optional PLUS Rabbit Stage- 6 x 26.5 x 1/4in. Maximum Travel: o X-RAD SmART and X-RAD SmART PLUS Vertical Y Stage Total 11in. (280mm) : ± 5.5in. (140mm) travel from isocenter Transverse X Stage Total 10in. (250mm) : ± 5in. (125mm) travel from isocenter Sagittal Z Stage Total 9in. (230mm) : ± 4.5in.(105mm) travel from isocenter 7

8 o X-RAD SmART MINI Vertical Y Stage Total 5in.(125 mm) : ±2.5in( 62.5mm) travel from isocenter) Transverse X Stage Total 5in.(125 mm) : ±2.5in( 62.5mm) travel from isocenter) Sagittal Z Stage Total 5in.(125 mm) : ±2.5in( 62.5mm) travel from isocenter) Travel limit and home detection proximity switches on all axis 4.3. Rotational Stage (2015) A rotational stage has been developed in order to deliver treatments at non-coplanar angles. By employing this stage, up to three animals can be simultaneously rotated about a vertical axis. This option will be available in Imaging Hardware & Specifications: Images are captured using an amorphous silicon flat panel detector mounted on the gantry. During image acquisition, a shutter mounted above the detector is opened, and then closed again prior to treatment to protect the detector from high energy x-rays Digital X-ray Detector A Perkin Elmer detector is mounted on the gantry opposite the X- ray source at a distance (SDD) of approximately 60 cm. This high quality detector has the following characteristics. Active pixels: (1024 x 1024) Pitch: 200 μm Total Area: 20 cm x 20 cm System Magnification Factor: 2 Voxel resolution at Isocenter: 100µm Imaging Volume at Isocenter:10 x 10 x 10 cm Capture Speed: 15 fps (30 200µm voxels) Scintillator: CsI Fastest 3D Acquisition/Reconstruction Time: 20 seconds Geometric Linearity: 0.5 mm over 100 mm Typical Imaging Dose: 1-10 cgy (center of 30 mm subject) Targeting accuracy: ±0.25 mm (standard mode), ±0.1 mm (high precision mode) 5.2. Detector Shutter A single leaf shutter is electrically driven using a ball-screw shaft mechanism. The purpose of the shutter is to protect the digital detector during high dose exposures during treatment. The shutter is controlled automatically by the Pilot software application. 6. Pilot Workstation Pilot, the Image Acquisition and Reconstruction, 3D alignment and Targeting Software, is licensed by the University Health Network (UHN) in Toronto Canada. Although many of the algorithms and methods are used clinically at UHN, they have developed a software suite specifically for the X-RAD SmART IGRT system. 8

9 6.1. Workstation Hardware A Dell model Precision T7500 with 6-core processor, 16GB of RAM, and a large HDD is supplied for image processing and motion control. Operating system will be Windows 7 Professional, upgradable to Windows 10. An optional display monitor can be added for an internal web-cam if requested. As technology improves, the basic specifications indicated will be upgraded. 7. Dosimetric Properties The X-RAD SmART system is capable of quickly delivering accurate radiation doses to specimens in tightly collimated beams for high throughput when conducting animal studies. By employing a robust calibration procedure (see section 8.1), the system is capable of accurately delivering radiation to a specified target. Typical dose rates for a 3 kw system are shown below for each collimator (for the 4.5 kw system, multiply by 1.5): Collimator Dose Rate (Gy/Min) Collimator Dose Rate (Gy/min) Open Field (10x10cm) x 40 mm mm Circular x 20 mm mm Circular x 15 mm mm Circular x 20 mm mm Circular x 10 mm mm Circular x 12 mm mm Circular 1.66 Additionally, geometric calibrations are performed in order to deliver maximum accuracy in positioning the treatment isocenter accurately. Using the flat panel detector, the position of a targeting BB is placed at isocenter relative to the center of a given collimator while irradiated with the treatment (large) focal spot. The stage is then moved according to any measured system flex to account for any differences at each angle. The figure below shows a post-calibration delivery of a star shot, where 8 even spaced beams were delivered for 90s on a piece of gafchromic film placed parallel to the incident beams: 9

10 8. Pilot Calibration, Acquisition and Reconstruction Software Pilot is the main user interface for the X-RAD SmART Radiation Research Platform. It was specifically developed for the X-RAD SmART by David Jaffray s team of researchers and developers at Princess Margaret Cancer Center to provide a user friendly interface to acquire images and deliver precision treatments. Scans and treatments are organized in a searchable database and organized by researcher and study. Treatment protocols and scan presets can be easily created or shared collaboratively with researchers within your institution or other institutes with X-RAD SmART systems. Pilot Start Page. For more information; refer to the X-RAD SmART Users Manual. 10

11 8.1. PilotCal Application Careful calibration of the imaging, mechanical and treatment systems is necessary for optimal system performance. In addition, monthly and biannual quality assurance tasks must be completed to ensure continued optimum performance. PilotCal provides a user friendly interface to run and track all necessary calibration and QA procedures. Below is a screen shot displaying the interface for performing a Winston Lutz Test for targeting calibration purposes. PilotCal Calibration Software - Calibration, Winston-Lutz For more information; refer to the X-RAD SmART Users Manual. 11

12 8.2. Fluoroscopic Image Guidance and Quick Treat Options Large institutions typically have users that require basic irradiation exposures in addition to complex, multi-beam treatments. Pilot makes it easy to perform rapid treatments (such as whole body irradiation or AP/PA treatments) using the fluoroscopic image guidance. Users can quickly move the X-ray source to a desired angle, position the specimen, and treat. It is also possible to perform portal imaging with the collimator in place to ensure accurate animal positioning. Fluoroscopic Image Acquisition and Stage Control Fluoroscopic Viewer and Stage Control For more information; refer to the X-RAD SmART Users Manual. 12

13 8.3. Pilot CBCT Scan Application Acquiring cone beam computed tomography (CBCT) scans is necessary to precisely place the isocenter to the treatment location and visualize the internal structure of specimens. Scan resolution can be as high as 100µm, and scans can be acquired in as little as 20 seconds. Acquired images are displayed in real-time. The targeting isocenter is placed by clicking and dragging the targeting widget to the appropriate location within the acquired CBCT scan. Once the isocenter is set, treatment plans are delivered at the click of a button. PilotXRAD Screenshot Following CBCT Acquisition, Isocenter indicated by Green Target For more information; refer to the X-RAD SmART Users Manual. 13

14 9. Treatment Planning Software Complex treatments typically require precise and accurate treatment planning. There are currently two options available for the X-RAD SmART for those interested in performing complex multibeam treatments for optimal dose delivery conditions Developed in collaboration with: PXI have entered in collaboration with MAASTRO Radiotherapy Clinic to develop Small Animal RadioTherapy (SmART) Plan, a treatment planning system developed specifically for use in preclinical specimens. Situated in Maastricht, the Netherlands, Maastro Clinic is one of Europe s leading cancer centers, and also a world leader in planning systems for small animal research. SmART Plan, using State-of-the-Art Monte Carlo algorithms (EGSNRC licensed from the National Research Council in Ottawa, Canada) to calculate dose, provides complex beam planning, dose calculation and visualization tools to enable researchers to accurately plan, visualize, and ultimately optimize treatment dose prior to therapy. SmART Plan Beam Planning with Multiple Beams and Isocenters, Brain Tumor Study 14

15 SmART-Plan Dose Visualization, Brain Tumor Study The system is compatible with all available X-RAD SmART collimators, and is capable of planning and delivering treatments with multiple static beams, dynamic arcs, and targets. Though plans can be easily concocted using the SmART Plan s user-friendly interface, advanced users can also dig deep in optimizing Monte Carlo algorithms based on speed, accuracy and precision. Additionally, as shown above, both tumors and any anatomical structures can be contoured prior to treatment calculation. Dose volume-histograms for these contoured structures are then displayed, and the plan can be optimized to deliver radiation therapy to certain regions (such as tumors) and avoid others (such as sensitive internal organs). 15

16 9.2. Open Source Treatment Creation System (Included at no charge) A free MATLab based treatment planning system is provided as an open source shareware application with each system. As part of the ongoing development of tools for small animal IGRT, UHN has developed a MATLab based treatment creation application for defining complex treatments using the images available from the X-RAD SmART. Below is an image from a multiangle treatment plan created using the Treatment Creation System. Open Source Treatment Creation Application The Treatment Creation application and all MATLab source code are provided with the X-RAD SmART system. Any future or collaborative improvements to this application can be implemented by anyone familiar with MATLab. 16

17 10. Co-Pilot Image Fusion using XVI Developed in collaboration with the Netherlands Cancer Institute (NKI), an image fusion package known as Co-Pilot, which employs XVI (the same software employed in Elekta clinical LINACs), is capable of fusing images from different datasets. This technique is primarily employed when delivering radiation therapy across multiple fractions. To maximize consistency, the treatment isocenter is defined on a reference image acquired on the first day of treatment, and subsequent images are matched accordingly to deliver the treatment to the same location. Co-Pilot can also be used to fuse images of multiple mice needing the same treatment plan allowing complex plans to be delivered quickly to multiple specimens. Another important feature is the software s ability to fuse multiple image sets from the same experiments or specimens. This is especially valuable during studies employing fractionated radiation delivery to a common isocenter, where it is extremely important to accurately deliver the same dose distribution at each fraction. XVI is a clinical software package that has been adapted to micro-ct geometry for use with the X- RAD SmART system. It serves to match images of the same specimens from different scans, be they acquired on CT, MRI, or other imaging platforms, to scans acquired using the X-RAD SmART system. This added functionality enables more accurate targeting in cases where tumour anatomy is difficult to observe in CBCT (such as embedded soft tissue tumours). XVI matches a scan image to a previously acquired reference image. The reference image can be a scan acquired by the X-RAD SmART, or imported from a different scanner, and is used to determine the location of the proposed treatment isocenter. The scan image is a recently acquired image from the X- RAD SmART scanner, used to locate the position of the current imaging isocenter. Fusion Example: Matching an MRI image to a scan from the X-RAD SmART using Co-Pilot 17

18 11. Integrated Bioluminescent Imaging Module Additionally, there is the possibility of adding fully integrated bioluminescent imaging to the X-RAD SmART, providing additional imaging capabilities beyond CBCT. This system is capable of visualizing injected optical contrast agents within preclinical specimens. Oftentimes, these agents are linked to tumor cells, enabling the visualization of tumors that would not normally appear under CBCT. Additionally, tumor viability can be directly correlated with the signal emitted from the optical contrast agents, allowing longitudinal tracking of tumor viability. Below is an image of the integrated system mounted to the gantry ring within the X-RAD SmART cabinet Combining bioluminescent imaging with IGRT The goal is to combine the anatomical information obtained from CBCT the functional information obtained from optically imaged contrast agents. This is used to improve targeting registering the optical signal with the CBCT data will accurately display the position of the tumor. Additionally, tumor response can be measured longitudinally with this imaging system, allowing for viability tracking during fractionated experiments. This is illustrated in the figure below: 18

19 11.2. Optical Imaging System Specifications Combining Optical Imaging and CBCT Technical Data Technology: Electron Multiplier CCD Lens Size: 50 mm F-Number: 0.95 FOV at Isocenter: 9.7 cm Resolution at Isocenter: 0.4 mm (max 0.2 mm) Distance from Lens to Isocenter: 25 cm Adjustable Focus and Aperture selection Support for multiple wavelengths: -Bundled with the following filters: nm, 607 nm, 624 nm, 655 nm -Replaceable filters for custom experiments 19

20 Optical signal overlaid on white light, fluoroscopic, and CT surface models of mouse images 12. Collaborative Development and Academic Research Team Access: The X-RAD SmART is a fully functional, high accuracy, IGRT system that is designed to be a flexible platform allowing research groups to build or add additional capabilities to an existing system. Both PXI and UHN have stressed the importance of providing current and future users with access to new developments and upgrades as they are completed, and to provide as open a platform as possible to allow expansion of the current technology. We encourage other research centers to collaborate with each other to improve the tools and techniques which ultimately will benefit all. The collaborative nature of this shared technology goes beyond software and hardware. The Biological experimental guidance currently being offered by researchers like Dr. Richard Hill and Dr. Brad Wouters, and the Medical Physics teams headed by Dr. David Jaffray and Dr. Frank Verhaegen will continue to stimulate future research direction and collaborative participation using the X-RAD SmART. Users Group Meetings are currently planned for the ASTRO and AAPM Annual Meetings. Previous meetings have been highly successful in stimulating development of new tools and methods, as well as presenting research results by those using the platform. 20