8/3/2016. CAMPEP Accredited, 2016!! CHERENKOV IMAGING IN RADIOTHERAPY: 2D, 3D, REALTIME 3D, Disclosure
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1 CHERENKOV IMAGING IN RADIOTHERAPY: 2D, 3D, REALTIME 3D, Real time IMRT Real time MRI/Co Whole breast radiotherapy Total skin therapy Brian W. Pogue PhD Engineering, Physics, Surgery, Dartmouth College CAMPEP Accredited, 2016!! Disclosure Brian Pogue is founder and President of DoseOptics LLC, developing the a commercially viable imaging system for radiotherapy. The company is NIBIB SBIR funded. 1
2 Cerenkov Output 8/3/2016 Imaging Water tank - 2D real time (Varian & ViewRay) - 3D tomography - 3D real time Patient imaging 2D Total Skin - 2D + CT Breast light emission Charged particle polarizes the dielectric Movement torques the dielectric High energy electrons produce light during dose deposition photons per e - Results from GEANT4 Monte Carlo Simulation Electron energy [MeV] Threshold Energy 220 kev Axelsson et al, Med Phys (2011) Glaser et al, Phys Med Biol (2015) 2
3 Time 8/3/2016 emission vs tissue depth Characteristic spectrum spectrum in tissue Tissue phantom 1% blood + 1% Intralipid oxygenated De-oxygenated Zhang et al, Med. Phys Axelsson et al, Med. Phys Single photon imaging: camera choices? ICCD: Amplify & then detect/readout EMCCD: Detect & then amplify/readout 1 pulse 5 pulses 15 pulses Andreozzi et al, Med Phys micro.magnet.fsu.edu Single photon imaging: camera choices? sec CCD Cooled CCD EMCCD ms ms CMOS scmos Intensified Camera ns Intensified Signal/Noise per Area Andreozzi et al, Medical Physics (2015) 3
4 Intensity Camera on 8/3/2016 Imaging LINAC pulses with time-gated ICCD LINAC LINAC Pulses 360Hz 360Hz Time Room Light Single photon counting with the room lights on! Beam images rejecting room light Glaser et al, Opt. Lett, 2012 Time Intensifier gain (10,000X) Time gated - 3us LINAC pulses Wavelength filtering Spatial median filter Temporal median filter Background subtraction online Real-time 2D Beam Imaging Adam Glaser PhD Glaser et al, Med. Phys. (2014) Real-time 2D+ or 3D Radiotherapy Beam Imaging 2D + time imaging 3D static imaging Adam Glaser PhD Glaser et al, Med. Phys. (2014) 4
5 PDD Water Tank Imaging: doping with quinine Quinine Sulfate added Accurate PDD 1 g/l angular emission at 41 degrees Glaser et al, Med. Phys. (2014) Real-time radiotherapy beam imaging (IMRT C-shape Plan) Video Time-integrated Glaser et al, Med. Phys. (2014) Gamma Analysis ( > 95% pass rate for 3% / 3 mm) Dose Plan Gamma % IMRT Dose Plan Gamma % VMAT 5
6 Temporal Analysis of VMAT Planning Target Volume (PTV) Organ at risk (OAR) MRI-radiation therapy: ViewRay (Washington Univ.) 2D Dosimetry imaging in high B-fields! Andreozzi et al, AAPM 2016, TU-AB-BRA-12 Prof Olga Prof Harold Jacqueline Green PhD Li PhD Andreozzi Petr Bruza PhD MRI-radiation therapy: ViewRay (Washington Univ.) 2D Dosimetry imaging in high B-fields! Lateral profiles at Dmax Andreozzi et al, AAPM 2016, TU-AB-BRA-12 Prof Olga Prof Harold Jacqueline Green PhD Li PhD Andreozzi Petr Bruza PhD 6
7 MRI-radiation therapy: ViewRay (Washington Univ.) 2D Dosimetry imaging in high B-fields! Real time beam delivery (40X sped up) Time-integrated delivery Andreozzi et al, AAPM 2016, TU-AB-BRA-12 Prof Olga Prof Harold Jacqueline Green PhD Li PhD Andreozzi Petr Bruza PhD 3-D CHERENKOV IMAGING? 1. Rotational tomography 2. Combined EPID/ tomography Image Filtered Backprojection Reconstruction +x +y Y Jaw X X MLC Raw J Camera Data J a Y Jaw a w w MLC set up Filtered video LINAC head Reverse cone beam geometry Glaser et al, Medical Physics 2015 Glaser et al, Medical Physics
8 Rotational Cone Beam Tomography with Filtered Backprojection Reconstruction +x +y Y Jaw Raw Camera Data X X MLC J J a Y Jaw a w w Predicted 3D Dose MLC set up Filtered video LINAC head Reconstructed tomogram Gamma analysis 3% / 3mm Glaser et al, Medical Physics 2015 Glaser et al, Medical Physics D Beam Analysis: vs. Film, TPS & Diode Left side Inter-leaf leakage right side Jaw leakage Glaser et al, Medical Physics 2015 Glaser et al, Medical Physics 2015 Real-time 3D Dosimetry: 2D EPID + 2D 2D (x,z) dose water tank EPID iccd Combined imaging In real time! EPID 2D (x,y) dose Petr Prof Joerg Jacqueline Bruza PhD Rottmann PhD Andreozzi 8
9 2D (x,z) dose Real-time 3D Dosimetry: 2D EPID + 2D water tank EPID iccd 1) Perspective backprojection of EPID 2) PDD 3) Real time 3D volumes correction factor Real time 3D MLC projection 4D accumulated dose distribution TG119, 0.25x0.25x0.39mm voxel size x = EPID 2D (x,y) dose Petr Prof Joerg Jacqueline Bruza PhD Rottmann PhD Andreozzi Human Imaging with dose imaging of delivered surface dose in whole breast radiotherapy 2 tangential treatment beams Rongxiao Zhang, PhD Jarvis et al, IJROBP
10 dose imaging of delivered surface dose in whole breast radiotherapy 2 tangential treatment beams First real-time radiation dose ever visualized! Predicted Plan Jarvis et al, IJROBP Jarvis et al, IJROBP Raw Filtered Real time videos: 12 patient pilot trial Treatment planned doses vs. images Tx plan Zhang et al, Phys. Med. Biol
11 Specialized radiation dose imaging camera High resolution CMOS video rate readout Onboard FPGA processing Output direct images overlaid on video white light images Imaging at the right price point Real time Ongoing Clinical Trial Contour Comparison to Plan Integrated Signal Total Skin Irradiation Imaging Old treatment angles New treatment angles Andreozzi et al, Medical Physics (2016) 1 st prize, Young Investigator Award, AAPM, July
12 SUMMARY 1. is readily imaged, with background/noise suppression 2. Water tank dosimetry real time 2D, & static 3D real time 3D with EPID 3. Human dose delivery imaging trials ongoing whole breast, total skin 4. Commercial translation DoseOptics LLC 5. Molecular imaging high resolution luminescence imaging Alumni Radiation Oncology Harvard / BWH Rad. Oncol. Johan Axelsson, Ph.D. David Gladstone, Sc.D. Lesley Jarvis, MD PhD Colleen Fox, Ph.D. Joerg Rottmann PhD Adam Glaser, Ph.D. Thayer School of Engineering Washington U. Rad. Oncol. Rongxiao Zhang, PhD Petr Bruza, PhD. Jacqueline Andreozzi Sara Saunders Olga Green PhD Harold Li PhD DoseOptics LLC Head Phantom PhD Venkat Krishnaswamy VP Technology PhD Bill Ware, CEO MS Tianshun Miao, Software MS 12
13 melanin 8/3/2016 Correction factors for /Dose: Monte Carlo Study R. Zhang et al, J. Biophotonics (in press) Reflectance based correction for tissue optics blood Reflectance /Reflectance R. Zhang et al, J. Biophotonics (in press) 13
14 Normalized emission (A.U.) Normalized absorbance A.U. Intensity (A.U.) IR680RD IR700DX IR800CW PtG4 IRDye680RD IRDye700DX IRDye800CW PtG4 IRDye700DX IRDye800CW PtG4 cw PtG4 gating Intensity (A.U.) Intensity (A.U.) Intensity (A.U.) Wavelength nm Wavelength nm Wavelength nm Background (Only PBS) /3/2016 Sampling depth: Monte Carlo Studies R. Zhang et al, PMB, R. Zhang et al, Med Phys, Skin optical properties Layer1 Layer2 Layer3 Layer4 Layer5 Layer6 Layer7 Stratum Living papillary upper blood reticular deep blood net subcutaneous corneum epidermis dermis net dermis dermis dermis fat 20µm 80µm 150µm 80µm 1500µm 100µm 6000µm *Thickness values are known to fluctuate +/- 30% between individuals or between locations on the same individual. lightly pigmented moderately pigmented darkly pigmented I. V. Meglinski and S. J. Matcher, "Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions," Physiological measurement 23, (2002). CELSI with Fluorophores spectrally resolved (a) (b) Wavelength nm Wavelength nm (a) 10 6 IRDye680RD Concentration mm IRDye700DX IRDye700DX Fluorescence Absorption
15 Radiation dose (Gy) 8/3/2016 Factors affecting Luminescence imaging sensitivity Lines of Constant S/N Probe Concentration (mm) DIFFUSE TOMOGRAPHY SOFTWARE FOR MEDICAL IMAGING Simultaneous 3 mouse imaging 15
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