Medical Imaging Seminar Session 2


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Medical Imaging - Opportunities for Business Seminar

Session 2 Technology Showcase

Three technologies developed or enhances at the University of Leicester are presented

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Medical Imaging Seminar Session 2

  1. 1. 24.01.12 Henry Wellcome Building University of Leicester A Space IDEAS Hub Event In association with: Medical Imaging – Opportunities for Business
  2. 2. • A knowledge exchange project from the Space Research Centre of the University of Leicester • Feed expertise developed from space missions into commercial benefit for UK industry. • Delivering Innovative Design, Engineering, Analysis and Support (IDEAS) to your business. • Part financed by the European Regional Development Fund • UK companies can access and benefit from our technology and experience. If your organisation would like to benefit from our knowledge and expertise, please contact us at About Space IDEAS Hub
  3. 3. 11:35 Detectors for high speed photon imaging and timing Dr Jon Lapington 11:55 Single Molecule Imaging Technology Prof George Fraser 12:15 High Resolution SFOV Gamma Camera Systems for Medical Imaging Dr John Lees Session 2 – Technology Showcase
  4. 4. Dr Jon Lapington, Reader in Space Physics, University of Leicester Space Research Centre
  5. 5. Space Research Centre  Why photon counting?  How to image single photons  Microchannel plate detectors  HiContent  C-DIR  Applications  Conclusions
  6. 6. Space Research Centre  Provides the ultimate sensitivity  Extends dynamic range to lowest light levels  Capable of picosecond (or better) time resolution  Can provide of high resolution imaging  Necessary for time coincidence or energy discrimination techniques  Is intrinsically linear up to detector rate limit
  7. 7. Space Research Centre  Imaging technologies depend on photon energy  X-rays and γ-rays  produce measurable signal in silicon detectors e.g. CCD  Optical photons  only produce 1 to a few electrons in silicon  Require some form of preamplification – gain  Silicon devices under development, but..  Only vacuum tube devices combine: ▪ High resolution imaging ▪ Low dark noise ▪ High time resolution
  8. 8. Space Research Centre Farnsworth 1930 patent Development of resistive lead glass Technology (1950s) The Channeltron or channel electron multiplier Invention of the continuous dynode technique Miniaturization and duplication (1960s) The Microchannel plate Conductive coating Microchannel Plate Cross-section Incident Radiation - + Output Electrons HV
  9. 9. Space Research CentreMCP operation  Lead Glass MCP  Secondary emitter  Electrodes  High voltage supply  Vacuum  Readout device  Particle detection  Electron, ion  Neutron  Photon (vacuum)  Photon (optical)  Optical window  Vacuum tube Cross section through MCP detector Readout Device - + n OpticalWindow
  10. 10. Space Research Centre Specification  High throughput multi-channel photon-counting  Photon timing with 25 picosecond accuracy  Up to 1024 parallel detection channels  Throughput up to 10M count/sec/channel  Compact integrated detector system  Retrofit-able to biological microscopes  Application-specific adaptability  Programmable digital processing capability Techniques and Applications  Time resolved spectroscopies  Multi-channel TCSPC  FLIM, FRET, FCS, polarization anisotropy, Raman  High Content bio-assay  e.g. drug discovery, cell screening  confocal microscopy, optical tomography Ratio of detected flux to input flux 0 0.2 0.4 0.6 0.8 1 1.2 1.00E+05 1.00E+06 1.00E+07 1.00E+08 Counts/cm^2/s Outputrate/inputrate UK/CERN Collaboration  Detector know-how from Astronomy  Electronics expertise from Particle Physics  Tube design from UK’s top manufacturer  Life science expertise
  11. 11. Space Research Centre  Event charge is localized on resistive layer  Transient signal induced through dielectric  Dielectric substrate part of vacuum housing  Induced signal sensed by C-DIR readout  C-DIR - a capacitively coupled electrode array Capacitive division – breakthrough performance  A new concept in centroiding readouts  Purely capacitive – picosecond timing potential  No resistive noise – no partition noise  25 x 25 mm2 C-DIR – pattern capacitance of <8 pF!  Very low total noise (<200 e- rms at τ=250ns) → 1000 × 1000 pixel2 at 106 electrons.  Simple linear algorithm – minimal processing  Excellent linearity - utilize >80% of anode  Capacitances intrinsic in pattern geometry Applications  Wide-field fluorescence lifetime imaging (FLIM)  Photon-timing/imaging e.g. LIDAR, TOFPET, 3D  pptv trace gas measurement using BBCEAS  Quantum Imaging, Quantum astronomy  TOF mass spectrometry  Molecular dynamics  Ring Imaging Cherenkov detectors for sLHC, FAIR C-DIR – the “Capacitive Division Image Readout” Proof-of-concept prototype Prototype image data C-DIR equivalent circuit Optimised flex-PCB C-DIR readout Linearity simulation
  12. 12. Space Research Centre  Time correlated single photon counting  Pulsed, focussed laser  Laser spot scanned in x and y  Measure fluorescence decay time (x,y) by accumulating histogram  PMT or gated intensifier (CCD)  Fluorescence limited to 0.01 events per laser pulse with single channel PMT  HiContent detector (641024 ch)  Multiple photons per pulse, or  Multiple imaged areas (Multiwell plate)  High content, high throughput bioassay  drug discovery
  13. 13. Space Research Centre Figures courtesy Schwille, “Fluorescence Correlation Spectroscopy” ebook
  14. 14. Space Research Centre  Pixellated photon counting detector replaces CCD camera  Event timing allows  Image reconstruction  Observation of dynamic signals  Advantages  Ultimate sensitivity  Reduced dark noise  No pixel aliasing effects  Much higher time resolution Cucurbita; 6x6 Configuration vsWidefield; 20x Objective Data and figure courtesy of Prof. Nick Hartell,UoL BBSRC-funded project: DigitalConfocal Microscope For High Speed Microscopy
  15. 15. Space Research Centre Revision: Cavity RingDown Spectroscopy • Using a pulsed coherent light source • Cavity output tails off exponentially • No spectral information • Requires pulsed laser Laser Input Pulse Pulse in cavity Cavity output Intensity
  16. 16. Space Research Centre fibre-optic alignment mirrors • Photon-counting provides phase shift of modulated light source • Uses broadband LED light source (no laser reqd.) • Monitor LED source and cavity output simultaneously • Simultaneous measurement at multiple wavelengths • Discriminate multiple species simultaneously • Technique is can be self calibrating • Capable of parts per trillion sensitivity C-DIR MCP detector Broadband Cavity Enhanced Absorption Spectroscopy Broadband LED light source cavity
  17. 17. Space Research Centre  We have developed complementary readout systems to exploit microchannel plate performance envelope for single photon counting  HiContent: Pixellated detector system with parallel multichannel electronics (up to 1024 channels with picosecond timing and very high throughput – 2.5 Mcount/ch/s)  C-DIR: Flexible, lost cost system with intrinsic high time resolution and customisable imaging performance - very high spatial resolution or moderate resolution with high throughput  We’re now exploit opportunities in a range of applications in the life science and other fields
  18. 18. 11:35 Detectors for high speed photon imaging and timing Dr Jon Lapington 11:55 Single Molecule Imaging Technology Prof George Fraser 12:15 High Resolution SFOV Gamma Camera Systems for Medical Imaging Dr John Lees Session 2 – Technology Showcase
  19. 19. Space IDEAS Hub Workshop , 24th January 2012. Space Research Centre Department of Physics and Astronomy, Michael Atiyah Building, University of Leicester Single Molecule Imaging Technology GW Fraser e-mail Tel 0116 252 3542 (direct line) or 3491 (PA) 1. Superconducting Tunnel Junctions (STJs) to register the energy, position and arrival time of single optical photons by measuring the charge deposited in a tantalum superconductor at a temperature of 0.3K 2. Insights into the basic fluorescence process, coupled to in-depth knowledge of detector physics, leading to novel algorithms for microarray analysis ?
  20. 20.  Measurement of light fundamental to life sciences research  Current measuring devices (PMTs,CCDs) have major limitations Monochrome High noise Low sensitivity  Life Sciences need detectors with: The ability to scan entire colour spectrum, photon-by-photon Greater sensitivity Less noise and better linearity  Solution – the Superconducting Tunnel Junction (STJ) Developed by the European Space Agency (ESA) for optical astronomy Requires closed-cycle cooler capable of 0.3 K (or below!) Only coarse (12 x 10) pixel arrays available
  21. 21. S-CAM  Developed by Tone Peacock, Mike Perryman et al. at ESTEC, from 1992 onwards  Successfully employed for stellar and planetary astronomy on the William Herschel Telescope STJ
  22. 22. 0 1 2 3 4 5 6 7 8 9 10 1 1.5 2 2.5 3 Photon energy (eV) Alexa 594 Alexa 488 The detection of multiple fluorescent labels using superconducting tunnel junction (STJ) detectors G.W. Fraser*, J.S. Heslop-Harrison†, T. Schwarzacher†, A.D.Holland*, P. Verhoeve‡ and A. Peacock (*Space Research Centre, Department of Physics and Astronomy and Department of Biology†, University of Leicester, Leicester LE1 7RH, UK. ‡ Science Payloads Technology Division SCI-ST , Research and Scientific Support Department , Postbus 299, ESA/ESTEC, 2200 AG Noordwjik, The Netherlands.) Review of Scientific Instruments, Volume 74, September 2003.
  23. 23. 0 0.1 0.2 400 500 600 700 800 Wavelength (nm) Counts/10nm/second (a) Raw Spectra Second ESTEC Campaign – single pixel Tantalum STJ
  24. 24. 0 0.05 0.1 0.15 0.2 400 500 600 700 800 Wavelength (nm) Counts/10nm/second (b)Background Subtracted Spectra
  25. 25. Third ESTEC Campaign – 2010 Limitations of sparse pixel array
  26. 26. Time Series – Photobleaching and Glitches
  27. 27. N3x25 triple measurement All Red Green Blue
  28. 28. Sample I2 single colour STJ images (DAPI, A594, A488) after super- resolution and smoothing compared with simultaneous CCD imagery CCD
  29. 29. I8_1_DAPI_0001 I8_1H2AX_488 Sample I8 single fluorophore (top) and simultaneous pulse-height resolved measurements Blue Green
  30. 30. BioAstral Cooltronics
  31. 31. 2. Applications in Life Sciences 3. Requirement for closed-cycle cryogenic cooler 4. Requirement for Super Resolution Software 5. New Applications in Exoplanet Detection? 1.Novel Astronomical Detector Technology – the optical STJ
  32. 32. 0 1 2 3 4 5 0 5 10 15 20 n , Fluorophores/molecule S(n) Alexa 488 Fluorescein-EX Alexa 546 Self-quenching
  33. 33. MA plot after collapse of two-colour microarray data set on to “line of parity” and imposition of noise threshold
  34. 34. Estimating the size of the population of expressed genes by comparison with null (Gaussian) cumulative distribution
  35. 35. The Future of Biology is the Detection of Light Acknowledgements Trude Schwarzacher, Pat Heslop-Harrison, David Ray, David Gough, Alyson Reed Rob Limpenny, Gauthier Torricelli, Sarah Botterill, Simon Lindsay, Daniel Brandt Peter Verhoeve and Didier Martin
  36. 36. 11:35 Detectors for high speed photon imaging and timing Dr Jon Lapington 11:55 Single Molecule Imaging Technology Prof George Fraser 12:15 High Resolution SFOV Gamma Camera Systems for Medical Imaging Dr John Lees Session 2 – Technology Showcase
  37. 37. Dr John Lees University of Leicester High resolution SFOV gamma camera systems for medical imaging Medical Imaging - Opportunities for Business Due to confidentiality restrictions, this presentation is not available online
  38. 38. If your organisation would like to benefit from our knowledge and expertise, please contact us. Space IDEAS Hub W: E: T: 0116 229 7700 Follow us on: Thank you for your interest