2. 1 Physics & Instrumentation in Positron Emission Tomography Paul Vaska, Ph.D. Center for Translational Neuroscience Brookhaven National Laboratory July 21, 2006

3. 2 Non-invasive Medical Imaging Techniques n Anatomical X-ray CAT MRI Ultrasound n Functional “nuclear medicine” - SPECT, PET Optical fluorescence, … CAT X-RayMRI

4. 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

5. 4 Technical Challenges in PET Imaging n Radiochemistry - better tracers n Imaging Physics - better images by Detector design –Spatial resolution –Sensitivity Image processing –Corrections for physical effects –Image reconstruction algorithms n Data Analysis & Biological Modeling - better interpretation of images

6. 5 PET Imaging Overview - Synthesize radiotracer - Inject radiotracer - Measure gamma-ray emissions from isotope (~20-60 min) - Reconstruct images of radiotracer distribution (nCi/cc)

7. 6 + + + Nucleus Neutrons Protons Electrons Positron (  + ) Decay 18 F-FDG

8. 7  + Decay + + + + + + + + + Neutron-deficient isotopes can decay by emitting positrons +anti-neutrino positron Net effect: one proton replaced by neutron neutron anti-neutrino anti-neutrino positron positron

9. 8 Positron annihilation n Annihilation gives 2x 511 keV gamma rays 180 degrees apart Line of response n Positron range & gamma noncollinearity n Scanner is just a photon counter! Counts gamma-ray pairs vs. single gammas Time window ~ 1 ns 511 keV e+e+ e-e-

10. 9 Raw Data & Image Reconstruction 0  projection 00 180  90  90  projection image reconstruction “sinogram”

11. 10 Important Detector Properties - Spatial resolution -Directly controls spatial resolution in reconstructed image -Currently ~ 1 - 5 mm -Depth-of-interaction? -Reduces “parallax”

12. 11 Important Detector Properties - Detection efficiency (aka sensitivity, stopping power) -Reduces noise from counting statistics -Currently > ~ 30% (singles) 55M Events 1M Events

13. 12 Important Detector Properties Random (accidental) coincidence - Time resolution -Affects acceptance of random coincidences -Currently ~ 1 - 10 ns -Time-of-flight (TOF)? -c = ~ 1 ft/ns -Need << 1 ns resolution

14. 13 Important Detector Properties Scatter and Attenuation 511 keV - 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

15. 14 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 light is converted to an electrical signal & amplified Front-end electronics condition the signal for further processing Prototypical PET Detector Gamma Ray Optical reflector

16. 15 New Developments Detectors Multimodality imaging Specialized applications

17. 16 175 25 New Developments: Detectors Scintillators No perfect choice - tradeoffs Also practical qualities Rugged? Hygroscopic? Cost?

18. 17 New Developments: Detectors Photosensors Photomultiplier tubes Avalanche photodiodes Arrays, position-sensitive Compact but noisier Silicon photomultipliers Very new Best of both? APD array PMT SiPM

19. 18 New Developments: Detectors Solid-state detectors Direct conversion, no photodetector Great dE/E & spatial resolution Poorer timing & stopping power CZT Z 2 Z 1 S a2 S a1 Sc Sc        

20. 19 New Developments: Detectors Pb converters & ionization HIDACPb-walled straws (50 cm long)

21. 20 New Developments: Detectors 3D gamma-ray event positioning Depth of interaction Reduces parallax problem vs. LSO slab crystal holder APD decoupling capacitor HV filter capacitor Current- limiting resistor signal output connector SHV connector unused APD slot

22. 21 New Developments: Detectors Time of flight using LaBr 3 no TOF 300 ps TOF 1 Mcts5 Mcts 10 Mcts

23. 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

24. 23 RatCAP: Rat Conscious Animal PET n 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

25. 24 Architecture n 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 n Timestamp & Signal Processing Module Programmable real-time logic (FPGA) 1 ns bins (debugging, now 10 ns) n Data acquisition PCI card in standard PC Up to 70 MB/s = ~10 Mcps singles Offline software for coincidences, corrections, recon, … TSPM TDC PCI card ASIC optical differential RatCAP

26. 25 Architecture RatCAP TSPM LSO APD ASICs all interconnections 38 mm FOV 72 mm OD optical links to PCI high voltage 194 g data, clock, power 18 mm axial FOV

27. 26 Performance n Spatial resolution (FWHM @ CFOV) FBP: 2.1 mm MLEM: <1.5 mm n Energy resolution: 23% FWHM n Time resolution: 14 ns FWHM window = 30 ns n Sensitivity (point @ CFOV):0.7% Peak Noise Equivalent Count rate:14 kcps @ 5  Ci/cc 1st prototype: LLD = 150 keV average, variable

28. 27 Imaging Conditions n Anesthetized 250-350 g rats n Limited DAQ livetime >> long scans for statistics n Artifacts

29. 28 F-18 Fluoride Bone Scan n 1.3 mCi fluoride RatCAP microPET R4

30. 29 C-11 Raclopride n 1.8 mCi raclopride In the RatCAP

31. 30 C-11 Methamphetamine Time-activity curve for striatum

32. 31 Thanks! DOE OBER funding