PET Imaging in Medical Diagnostics: Physics and Instrumentation Overview

1. Physics & Instrumentation inPositron Emission Tomography Paul Vaska, Ph.D. Center for Translational Neuroscience Brookhaven National Laboratory July 21, 2006

2. Non-invasive Medical Imaging Techniques CAT MRI X-Ray • Anatomical • X-ray • CAT • MRI • Ultrasound • Functional • “nuclear medicine” - SPECT, PET • Optical fluorescence, …

3. Positron Emission Tomography Recent mainstream acceptance • relatively expensive • cyclotron for tracer production • detectors must stop high-energy gamma-rays • low resolution (>2 mm), limited counting statistics • BUT unique functional capabilities Applications • Diagnosis of disease • cancer (WB), cardiac, … • Research • brain function • animal studies

4. Technical Challenges in PET Imaging • Radiochemistry - better tracers • Imaging Physics - better images by • Detector design • Spatial resolution • Sensitivity • Image processing • Corrections for physical effects • Image reconstruction algorithms • Data Analysis & Biological Modeling - better interpretation of images

5. PET Imaging Overview • Synthesize radiotracer • Inject radiotracer • Measure gamma-ray emissions from isotope (~20-60 min) • Reconstruct images of radiotracer distribution (nCi/cc)

6. Nucleus Neutrons + + + Protons Electrons Positron (+) Decay 18F-FDG

7. + + + + + + + + + + + Decay Neutron-deficient isotopes can decay by emitting positrons anti-neutrino positron • Net effect: one proton replaced by • neutron • anti-neutrino • positron

8. Positron annihilation • Annihilation gives • 2x 511 keV gamma rays • 180 degrees apart • Line of response • Positron range & gamma noncollinearity • Scanner is just a photon counter! • Counts gamma-ray pairs vs. single gammas • Time window ~ 1 ns 511 keV e+ e- 511 keV

9. Raw Data & Image Reconstruction 0 90 180 “sinogram” 90 projection image reconstruction 0 projection

10. Important Detector Properties • Spatial resolution • Directly controls spatial resolution in reconstructed image • Currently ~ 1 - 5 mm • Depth-of-interaction? • Reduces “parallax”

11. 55M Events 1M Events Important Detector Properties • Detection efficiency (aka sensitivity, stopping power) • Reduces noise from counting statistics • Currently > ~ 30% (singles)

12. Random (accidental) coincidence Important Detector Properties • Time resolution • Affects acceptance of random coincidences • Currently ~ 1 - 10 ns • Time-of-flight (TOF)? • c = ~ 1 ft/ns • Need << 1 ns resolution

13. Important Detector Properties • Energy resolution • Scattered gammas change direction AND lose energy • Affects acceptance of scattered coincidences • Currently ~ 20% • Deadtime • Handle MHz count rates! 511 keV 400 keV 511 keV Scatter and Attenuation

14. Prototypical PET Detector Optical reflector light is converted to an electrical signal & amplified Gamma Ray Scintillation Crystal PMT Pre-Amplifier + Electronics Gamma photon converts to optical photons (proportional to gamma energy, typ. 1000’s) photons are collected at the end of the crystal Front-end electronics condition the signal for further processing

15. New Developments • Detectors • Multimodality imaging • Specialized applications

16. 25 175 New Developments: Detectors • Scintillators • No perfect choice - tradeoffs • Also practical qualities • Rugged? • Hygroscopic? • Cost?

17. New Developments: Detectors • Photosensors • Photomultiplier tubes • Avalanche photodiodes • Arrays, position-sensitive • Compact but noisier • Silicon photomultipliers • Very new • Best of both? PMT APD array SiPM

18. Sa1 Sa2 Z1 Z2         Sc New Developments: Detectors • Solid-state detectors • Direct conversion, no photodetector • Great dE/E & spatial resolution • Poorer timing & stopping power • CZT

19. New Developments: Detectors • Pb converters & ionization HIDAC Pb-walled straws (50 cm long)

20. vs. SHV connector decoupling capacitor signal output connector APD HV filter capacitor LSO slab unused APD slot Current-limiting resistor crystal holder New Developments: Detectors • 3D gamma-ray event positioning • Depth of interaction • Reduces parallax problem

21. 10 Mcts 1 Mcts 5 Mcts no TOF 300 ps TOF New Developments: Detectors • Time of flight using LaBr3

22. New Developments • Multimodality imaging • PET/CT • PET/MRI • Specialized applications • Brain, breast, prostate • Small animal - microPET • Arterial input function • Humans - wrist scanner • Animals - microprobe • Awake rat brain - RatCAP

23. RatCAP: Rat Conscious Animal PET • Eliminate anesthesia in preclinical neuroscience using PET in order to: • Remove confounding effects of anesthetic on neurochemistry • Enable stimulation in animal PET • Enable correlations of behavior and neuro-PET

24. RatCAP ASIC differential TSPM TDC optical PCI card Architecture • Detector blocks x12 • LSO 2.2 x 2.2 x 5 mm in 4 x 8 array • 1:1 coupling to APD • ASIC - single all digital output • Timestamp & Signal Processing Module • Programmable real-time logic (FPGA) • 1 ns bins (debugging, now 10 ns) • Data acquisition • PCI card in standard PC • Up to 70 MB/s = ~10 Mcps singles • Offline software for coincidences, corrections, recon, …

25. Architecture high voltage data, clock, power all interconnections LSO APD 18 mm axial FOV 38 mm FOV ASICs TSPM 72 mm OD optical links to PCI RatCAP 194 g

26. Performance 1st prototype: LLD = 150 keV average, variable • Spatial resolution (FWHM @ CFOV) • FBP: 2.1 mm • MLEM: <1.5 mm • Energy resolution: 23% FWHM • Time resolution: 14 ns FWHM • window = 30 ns • Sensitivity (point @ CFOV): 0.7% • Peak Noise Equivalent Count rate: 14 kcps @ 5 Ci/cc

27. Imaging Conditions • Anesthetized 250-350 g rats • Limited DAQ livetime >> long scans for statistics • Artifacts

28. F-18 Fluoride Bone Scan • 1.3 mCi fluoride RatCAP microPET R4

29. C-11 Raclopride • 1.8 mCi raclopride In the RatCAP

30. C-11 Methamphetamine Time-activity curve for striatum

31. Thanks! DOE OBER funding