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Precision X-Ray Inc. The Global Standard for Pre-Clinical

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Presentation on theme: "Precision X-Ray Inc. The Global Standard for Pre-Clinical"— Presentation transcript:

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2 Precision X-Ray Inc. The Global Standard for Pre-Clinical
Specimen X-ray Irradiation and Imaging Systems The Global Standard for Pre-Clinical X-Ray Irradiation and Imaging Research Systems! Headquarters: North Branford, CT, USA Incorporated: FOCUS : X-Ray Irradiation for Radiation Based Research Key Product Lines: Standard Products : X-RAD 160, 225, 320, 350 kV: Fixed Beam X-Ray Irradiation Systems X-RAD 320 : Workhorse of the Industry – 100’s Worldwide Introduced Since 2015 NEW : X-RAD SmART –3D Image Guided Small Animal Radiation Therapy System NEW: X-RAD 160, 225 and 320 XL/XLi family – Designed for High Throughput Irradiation and 2D Multimodal Imaging . Largest Irradiation Chambers NEW :OptiMAX - Optical and X-Ray Multimodal Imaging Modules for X-RAD XL/XLi Systems .

3 Specimen X-ray Irradiation Systems
X-RAD® Specimen X-ray Irradiation Systems The World Leader in X-Ray Systems for Pre-Clinical Radiation Research. High X-ray Peak Energies ( kV) The Largest Irradiation Chambers for Highest Throughput and Largest Animals Proven & Reliable Technology ’s of Systems In Use Worldwide Gamma Source Alternative Full line of Options & Accessories Continuous New Product Development

4 X-RAD Customer List in CA 2018
Precision X-Ray Inc. Specimen X-ray Irradiation and Imaging Systems The Global Standard for Pre-Clinical X-Ray Irradiation and Imaging Research Systems! X-RAD Customer List in CA 2018 USC, Los Angeles, CA ( X-RAD 320) University of California San Diego, CA (X-RAD 320) SRI International, Menlo Park, CA (X-RAD 320) Cedar Sinai Medical Center, Los Angeles, CA (X-RAD SmART) Lawrence Berkeley National Labs, Berkeley, CA (X-RAD 320) UCLA, Los Angeles, CA (X-RAD SmART) VA Northern California Healthcare, McClellan, CA (X-RAD iR160) Stanford University, Stanford, CA (X-RAD SmART) UC Irvine – Irvine CA ( X-RAD 320) University of Southern California, Los Angeles, CA (X-RAD 320ix) City of Hope, Los Angeles, CA (X-RAD 320) Bayer, San Francisco, CA (X-RAD 320) Stanford University, Stanford, CA (X-RAD 320) Pfizer, La Jolla CA, (X-RAD 225) University of California, Berkeley, CA (X-RAD 320) 2nd system University of California San Diego, La Jolla, CA (X-RAD 225XL) University of California, Berkeley, CA (X-RAD 320) City of Hope, Los Angeles, CA (X-RAD SmART) Henkel, Irvine, CA (X-RAD iR-225) VA Palo Alto, Palo Alto, CA (X-RAD 320) University of California – Riverside, Riverside, CA (X-RAD 320) Merck & Co, Palo Alto, CA (X-RAD 320) UCSD LaJolla CA ( X-Rad SmART) USC, Los Angeles, CA (X-RAD iR-160)

5 X-RAD SmART X-RAD 225Cx The SMART Generation Small Animal IGRT
3D imaging , planning and treatment delivery that mimics RT in the Clinic Flexible Cabinet Design to suit any laboratory size Large Chamber for Larger Animals Highest Dose Rate Modular assembly that is possible to disassemble in case of a move Very Higher Precision Gantry and Stage System CBCT and BLI Imaging Advanced Monte Carlo Treatment Planning Detailed Commissioning and Training New High Resolution MicroCT Module X-RAD SmART Cabinet Exterior

6 X-RAD SmART Small Animal “Image Guided” RT X-Rad 225Cx: Interior View
HT Safety Interlock for Door Service Access Door Control Electronics Cabinet Routine Access Door Radiation Warning Light U-arm and Drive Assembly Load-bearing Gantry Ring CsI:Tl a-Si:H Detector NDT X-ray Tube (5-225kVp) Detector-protecting Shutter and Drive Assembly Mouse

7 X-RAD SmART Small Animal IGRT
Multiple Mouse Imaging , Planning and Treatment

8 Specimen X-ray Irradiation Systems
X-RAD® 320/350 Specimen X-ray Irradiation Systems Industry Workhorse : 100’s Worldwide The X-RAD 320 is a self-contained X-ray irradiation system for high and low dose radiation studies normally conducted in research laboratories. Largest internal cabinet in smallest external footprint: NEW: Up to 33 mice at one time in three rotating pie cages . Orthovoltage X-Ray (5-320kV): Ideal for all cell and small animal irradiation studies. Optimal replacement for Cesium gamma sources. Dose Measurement & Control provides repeatable dose delivery. Many fixtures available for partial body irradiation, and specimen placement. Industry leader in small animal X-ray studies – 100’s of systems installed!

9 Cell and Animal-Adaptable Chamber
X-RAD® 320 Specimen X-ray Irradiation Systems Cell and Animal-Adaptable Chamber 320kV X-ray Tube Cold Light Lamp Interlock Adjustable Collimator Temperature Control Automated Filter Recognition Stainless Steel Shelf CO2&O2 Control Stainless Steel Inner-wall Motorized/ Programmable Shelf Elevator

10 X-RAD 320 Whole Body Irradiation of Mice
Precision X-Ray Inc. X-RAD 320 Whole Body Irradiation of Mice Single Rotating Stage Planetary Rotating Stage Pie Cage 86cm 50cm SSD 80cm SSD 86cm STANDARD Single Pie Cage 11 Mice 50cm SSD 320kVp, 12.5mA ~1Gy/ min 6Gy in 6 min NEW Triple Pie Cage 33 Mice 80cm SSD 320kVp, 12.5mA ~0.4Gy/ min 6Gy in 15min Max Beam Diameter 50cm Max Beam Diameter 50cm

11 OPTIONS AND ACCESSORIES
X-RAD 320® OPTIONS AND ACCESSORIES Partial Body Irradiation using Fixtures and Shields Standard holding fixtures and corresponding lead shield for mice Size 1 (<25g mice) Fixture Body Diameter is 1 in. (25mm) QUAD Fixture for Cranial Irradiation

12 OptiMAX M-IGRT X-RAD 320® Optical and X-Ray Molecular
Specimen X-ray Irradiation & Imaging Systems OptiMAX M-IGRT Optical and X-Ray Molecular Image Guided Radiation Therapy Available in NEW: X-RAD 160XL, 225XL and 320 XL Also in X-RAD 320 X-RAD 320/350

13 Optical Molecular and X-Ray Imaging Module
OptiMAX IGRT Optical Molecular and X-Ray Imaging Module High Sensitivity Luminescence and X-ray Imaging X-ray at 50kV Luminol Luminescence Overlaid on X-ray

14 Optical Molecular and X-Ray Imaging Module
OptiMAX IGRT Optical Molecular and X-Ray Imaging Module

15 Orthovoltage X-Ray Minibeams
X-RAD OXM Orthovoltage X-Ray Minibeams OXM Collimator Face Chromographic Film Merged Beams = Treatment Mini-Beams = Tissue Sparing

16 X-RAD SmART NEW Micro CT Module
Standard CBCT: Mouse Lungs - 0.4mm spot MicroCT: Mouse Lungs – 50micron spot

17 Regional Microdosimetric Variations in Bone Marrow for Photon Irradiation at Different Energies
Matthew Belley1, Milton R. Cornwall-Brady2, Markus Burkhart3, Mark Dewhirst1, Terry Yoshizumi1 and Julian D. Down2 1Duke University Medical Center, Durham, NC, 2Massachusetts Institute of Technology, Cambridge, MA, 3SCANCO Medical AG, Bruettisellen, Switzerland INTRODUCTION METHODS AND PROCEDURE High resolution scans (1 µm, µCT 50, SCANCO Medical) were performed on the femur and lumbar vertebrae from a C57BL/6 mouse Importance of Uniformity of Radiation Dose Radiobiological studies among different laboratories and centers need standardization of radiation dose. Apart from dosimetry to determine the actual absorbed dose in Gray (Gy), due consideration of differences in biological effect is needed at different energies. Relatively high energies (megavoltage of >500 Lower resolution scan (25 µm, µCT 50, eXplore CT120 Micro CT Scanner, GE Medical Systems) performed on the whole body of a C57BL/6 mouse Vertebrae (L2-5) Femur Vertebra KeV) are the most relevant to both exposures in clinical RT and from nuclear incidents. The escalating restrictions and costs of using gamma irradiators as imposed by security requirements have, however, prompted orthovoltage X-ray machines in experimental studies. Reasonable equivalency for a given biological effect X-rays to replace gamma-irradiators. the increasing use of per dose is warranted for Femur Majority of active BM is in cavities of trabecular bone. Scout Scout – Colvin et al., 2004. ~50% hematopoietic activity in vertebrae of the mouse Relative Biological Effectiveness (RBE) of X-rays vs. -rays Differences well-known for hematopoietic lethality in rodents (LD50/30): approximated at an RBE of 0.8 (orthovoltage X-rays ~20% more effective in dose - Sinclair & Blackwell, 1962) 1.0 mm Change in Relative Biological Effectiveness (RBE) with Radiation Energy Due to differences in average linear energy transfer (LET): 60Co -rays ~ 0.4 keV/m 137Co -rays ~ 0.8 keV/m 200 kVp X-rays ~3.5 keV/m Higher content of high LET delta rays for lower energy irradiation may produce more irreparable DNA damage. Differences may be enhanced with protracted low dose rate or fractionation. RESULTS Variations in BM Dose According to the Different Radiation Energies (Vertebra) Radiation Dose Contours – 1 mm Cu HVL = 85 keV X-Ray Energy Spectra (Precision Xrad 320 Machine) HVL = 1 mm Cu Due to differences in dose absorption: Photoelectric effect (orthovoltage) – dominant for materials of high atomic number (Z) Compton scattering (megavoltage) – absorption independent of atomic number Pair formation (supravoltage) - dominant for materials of high atomic number (Z) HVL = 4 mm Cu 137Cs -rays Vertebra Lower Resolution - Monte Carlo Simulation with Micro-CT – 225 kVp X- rays from XRad225Cx machine, Precision X-Ray Inc – from Chow et al. Med Phys. 2010;37: Relative dose increase in the BM compared to the dose at “Equilibrium” depth Radiation Dose Increase at Different BM Volumes x3 higher dose to bones 360° photon arc and 0.3 mm Cu filter through mouse thorax. HVL = 1.0 mmCu (Newton et al. Med Phys. 2011;38: ) 100% HVL = 1 mm Cu Average dose increase = 1.33 Percent BM Volume 80% F1 F8 Cs-137 HVL = 4 mm Cu Average dose increase = 1.08 137Cs -rays Average dose increase = 0.98 60% Future Analysis - Estimate absorbed dose in BM for different energies for whole skeleton –from whole body scan (eXplore CT120 Micro CT Scanner, GE Medical Systems) 1.0 2.0 5.0 4.0 3.0 10 14 Al Cu HALF VALUE LAYER (mm) RELATIVE ABSORBED DOSE (f) MUSCLE WATER PHOTON ENERGY (MeV) High radiation absorption occurs in bone (Z = 13) due to photoelectric effect at effective energies below 150 keV (>4 mm Cu HVL) - Jaeger & Harnisch, 1983 -rays 137Cs 60Co 320 kVp X-rays F1 Filter BONE 320 kVp X-rays F8 Filter 40% 20% 0% Relative Dose Increase Agrees with Existing Biological Data - Differences in Radiation Cell Survival for Hematopoietic Progenitors (CFU-C) in Bone Marrow and Spleen and Stromal Progenitors (CFU-F) in Bone Marrow with 60Co -rays vs. 200 kVp X-rays (HVL = 1.05 mmCu) – Beekman & Down, unpublished CONCLUSIONS To obtain biological effects that best model exposures from either clinical radiotherapy or nuclear incidences, X-rays of highest potential energy and filtration should be used. Absorption in bone at low effective radiation energies and the consequent high doses to neighboring bone marrow due to the photoelectric effect is especially problematic in studies involving radiation effects on the hematopoietic system. For the Precision XRAD 320 machine, the F8 filter (1.50 mm Al mm Cu mm Sn) has an HVL of ~4.0 mm Cu at 320 kVp and is close to effects of 137Cs or 60Co -rays. The “inconvenient” decrease in dose-rate with added filtration has to be accepted as long as it does not allow repair of sub-lethal damage at below 0.5 Gy/min. These effects may be exploited to locate the hematopoietic stem cells and progenitors in relation to distance from bone and resolve the relative contribution of the endosteal and vascular niche hypotheses. 1 Surviving Fraction 0.1 X BM CFU-F 0.01 X CFU-C Spleen 0.001 X BM CFU-C METHODS AND PROCEDURE 0.0001 M• onte-Carlo Simulations Radiation Dose (Gy) Can Adress Current Controversy on Location of the Hematopoietic Stem Cell Niche in Bone Marrow Simulated a mouse body using a 2.5cm diameter cylinder of water Validated the physics settings by performing a “planar” simulation of a GATE Software Used (Geant4 Application for Tomographic Emission) bone/spleen interface Endosteal Stem Cell Niche Vascular Stem Cell Niche phantom Placed the Scanco vertebra and femur phantom models into this water 5 micron resolution for the femur and vertebra REFERENCES The vertebra and femur were positioned in the cylindrical water phantom according to the actual anatomy of micro-CT images of whole mouse (eXplore CT120 Micro CT Scanner, GE Medical Systems) HSC HSC Ellis RE. Some experiments relating to dose in a model of trabecular bone. Br J Radiol. 1966;39:211-5. Gengozian N, Taylor T, Jameson H, Lee ET, Good RA, Epstein RB. Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate. Radiat Res. 1986;105:320-7. King SD, Spiers FW. Photoelectron enhancement of the absorbed dose from X rays to human bone marrow: experimental and theoretical studies. Br J Radiol. 1985;58: Jaeger SS, Harnisch BD. Corrected f factors for photons from 10 keV to 2 MeV. Med Phys. 1983;10:714-6. Sinclair WK. The relative biological effectiveness of 22-Mevp x-rays, cobalt-60 gamma rays, and 200-Kvcp x-rays. V. Absorbed dose to the bone marrow in the rat and the mouse. Radiat Res. 1962;16:369-83 Colvin GA, Lambert JF, Abedi M, Hsieh CC, Carlson JE, Stewart FM, Quesenberry PJ. Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology. Leukemia ;18: Xrad-320 geometry - 50cm Source-Object Distance. Beam entered mouse on dorsal side Bone Osteoblast Number of particles simulated: 10e9 source particles Endothelial Cell Materials – bone was set to “rib bone” and marrow was set to “spleen” Three energy beams simulated: 320 kVp X-rays at 1mm Cu (85 keV) and 4mm Cu HVL (150 keV) and Cs-137 -rays (662 keV). Next to bone - Higher radiosensitivity at low energy irradiation Far from bone - Lower radiosensitivity at low energy irradiation

18 Microdosimetric Variations in Bone Marrow for Photon Irradiation at Different Energies
Belley et. al. .. Duke

19 Microdosimetric Variations in Bone Marrow for Photon Irradiation at Different Energies
Belley et. al. CONCLUSIONS - Excerpt To obtain biological effects that best model exposures from either clinical radiotherapy or nuclear incidences, X-rays of highest potential energy and filtration should be used. Absorption in bone at low effective radiation energies and the consequent high doses to neighboring bone marrow due to the photoelectric effect is especially problematic in studies involving radiation effects on the hematopoietic system. For the Precision XRAD 320 machine, the F8 filter (1.50 mm Al mm Cu mm Sn) has an HVL of ~4.0 mm Cu at 320 kVp and is close to effects of 137Cs or 60Co -rays.

20 Replacement of Gamma Irradiators
With X-RAD320 Summary: Replacement of CsCl Research Irradiators with X-ray Irradiators “We performed an analysis of the current line of x-ray research irradiators compared to the CsCl research irradiators against four performance parameters (dose rate, field size, depth-dose, and RBE) and found that the x-ray irradiators provided equivalent performance in terms of dose rate, irradiation field size, and uniformity over the field. Depth-dose for the (X-RAD) 320 kV x-ray irradiator was nearly identical to that of CsCl down to a depth in tissue of 4 cm while the 160 kV x-ray machine could produce similar depth-dose as CsCl only to a depth of less than 2 cm. This indicates that the 320 kV x-ray machine has broader application to both cell culture irradiation and mouse irradiation while more careful research setup is required if the lower voltage x-ray machines are used for mouse irradiation.” Excerpt from Sandia National Laboratories Draft Report: Cesium Chloride Irradiator Replacement Study: Replacement Costs and Alternative Technologies


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