1. Synergies Between Calorimetry and PET William W. Moses Lawrence Berkeley National Laboratory March 26, 2002 Outline: –Fundamentals of PET –Comparison of Calorimetry & PET –Areas of Common Interest –Conclusions

2. Step 1: Inject Patient with Radioactive Drug Drug is labeled with positron (  + ) emitting radionuclide. Drug localizes in patient according to metabolic properties of that drug. Trace (pico-molar) quantities of drug are sufficient. Radiation dose fairly small (<1 rem). Drug Distributes in Body

3. Ideal Tracer Isotope 18 F 2 hour half-life 15 O, 11 C, 13 N2, 20, & 10 minute half-lives 18 F 2 hour half-life 15 O, 11 C, 13 N2, 20, & 10 minute half-lives Interesting Biochemistry Easily incorporated into biologically active drugs. 1 Hour Half-Life Maximum study duration is 2 hours. Gives enough time to do the chemistry. Easily Produced Short half life  local production.

4. Step 2: Detect Radioactive Decays Ring of Photon Detectors Radionuclide decays, emitting  +.  + annihilates with e – from tissue, forming back-to-back 511 keV photon pair. 511 keV photon pairs detected via time coincidence. Positron lies on line defined by detector pair (known as a chord or a line of response or a LOR). Detect Pairs of Back-to-Back 511 keV Photons

5. Multi-Layer PET Cameras Can image several slices simultaneously Can image cross-plane slices Can remove septa to increase efficiency (“3-D PET”) Planar Images “Stacked” to Form 3-D Image Scintillator Tungsten Septum Lead Shield

6. Step 3: Reconstruct with Computed Tomography 2-Dimensional Object By measuring all 1-dimensional projections of a 2-dimensional object, you can reconstruct the object By measuring all 1-dimensional projections of a 2-dimensional object, you can reconstruct the object 1-Dimensional Vertical Projection 1-Dimensional Horizontal Projection

7. Why Do Computed Tomography? Planar X-RayComputed Tomography Images courtesy of Robert McGee, Ford Motor Company Separates Objects on Different Planes

8. Attenuation Correction Use external  + source to measure attenuation. Attenuation (for that chord) same as for internal source. Source orbits around patient to measure all chords. Measure Attenuation Coefficient for Each Chord Obtain Quantitative Images Measure Attenuation Coefficient for Each Chord Obtain Quantitative Images  + Source

9. Time-of-Flight Tomograph Can localize source along line of flight. Time of flight information reduces noise in images. Time of flight tomographs have been built with BaF 2 and CsF. These scintillators force other tradeoffs that reduce performance. c = 1 foot/ns 500 ps timing resolution  8 cm fwhm localization Not Compelling with Present Technology...

10. NMR & PET Images of Epilepsy NMR “Sees” Structure with 0.5 mm Resolution PET “Sees” Metabolism with 5.0 mm Resolution NMRPET

11. PET Images of Cancer Metastases Shown with Red Arrows Brain Heart Bladder Normal Uptake in Other Organs Shown in Blue Treated Tumor Growing Again on Periphery

12. PET Camera Design Typical Parameters Detector Module Design

13. PET Cameras Patient port ~60 cm diameter. 24 to 48 layers, covering 15 cm axially. 4–5 mm fwhm spatial resolution. ~2% solid angle coverage. $1 – $2 million dollars. Images courtesy of GE Medical Systems and Siemens / CTI PET Systems

14. Early PET Detector Element BGO Scintillator Crystal (Converts  into Light) Photomultiplier Tube (Converts Light to Electricity) 3 — 10 mm wide (determines in-plane spatial resolution) 10 — 30 mm high (determines axial spatial resolution) 30 mm deep (3 attenuation lengths)

15. Modern PET Detector Module BGO Scintillator Crystal Block (sawed into 8x8 array, each crystal 6 mm square) 4 PMTs (25 mm square) 50 mm 30 mm Saw cuts direct light toward PMTs. Depth of cut determines light spread at PMTs. Crystal of interaction found with Anger logic (i.e. PMT light ratio). Good Performance, Inexpensive, Easy to Pack

16. Crystal Identification with Anger Logic Can Decode Up To 64 Crystals with BGO X-Ratio Y-Ratio Uniformly illuminate block. For each event, compute X-Ratio and Y-Ratio, then plot 2-D position. Individual crystals show up as dark regions. Profile shows overlap (i.e. identification not perfect). Profile through Row 2

17. Fundamental Limits of Spatial Resolution Dominant Factor is Crystal Width Limit for 80 cm Ring w/ Block Detectors is 3.6 mm Dominant Factor is Crystal Width Limit for 80 cm Ring w/ Block Detectors is 3.6 mm

18. Tangential Projection Radial Elongation Penetration of 511 keV photons into crystal ring blurs measured position. Effect variously known as Radial Elongation, Parallax Error, or Radial Astigmatism. Can be removed by measuring depth of interaction. Radial Projection

19. PET Front End Electronics Analog ASIC Custom ASIC PMT A PMT B PMT C PMT D Energy ADC FPGA X ADC Y Time TDC RAM Off the Shelf “Singles” Event Word Position Time Digitize Arrival Time (latch 500 MHz clock — 2 ns accuracy) Identify Crystal of Interaction & Measure Energy Correct Energy and Arrival Time (based on crystal) Maximum “Singles” Event Rate is 1 MHz / Detector Module If Energy Consistent with 511 keV, Send Out “Singles” Event Word (Position & Time)

20. PET Readout Electronics FPGAs Fiber Optic Interface Off the Shelf “Coincidence” Event Word Location of Chord Singles 0 Search for “Singles” in Time Coincidence (~10 ns window) Strip Off Timing Information Format “Coincidence” Event Word (chord location) Maximum “Coincidence” Event Rate is 10 MHz / Camera Search for Coincidences, Send Out “Coincidence” Event Word (Position of Chord) Singles n...... From Each Camera Sector

21. Similarities and Differences Between Calorimetry & PET Similarities The PET World Picture...

22. Similarities Between Calorimeters and PET PET Camera Calorimeter Cylindrical Gamma Ray Detectors High Efficiency, Hermetic Segmented, High Density Scintillator Crystals High Performance Photodetectors High Rate, Parallel Readout Electronics

23. The PET World Picture: Signal Levels Are Very Low *511 keV Need to Image 0.000000511 TeV* Photons

24. No Pair Production / EM Showers Compton scatter in patient produces erroneous coincidence events. ~15% of detected events are scattered in 2-D PET (i.e. if tungsten septa used). ~50% of events are scattered in 3-D Whole Body PET. Compton Scatter is Important Background Use Energy to Reject Scatter in Patient Compton Scatter is Important Background Use Energy to Reject Scatter in Patient Scatter Length ≈ 10 cm

25. Patient Radiation Dose is Limited! Cannot Increase Signal Source Strength Image Noise Is Limited by Counting Statistics Cannot Increase Signal Source Strength Image Noise Is Limited by Counting Statistics

26. Competitive Commercial Market Cost is Very Important $60 Million (parts cost) 72,000 Channels $833 / Channel $1 Million (parts cost) 18,400 Channels $54 / Channel CMS CalorimeterPET Camera Scintillator crystals are ~25% of total parts cost Photomultiplier tubes are ~25% of total parts cost No other component is >10% of total parts cost In a PET Camera:

27. PET Detector Requirements Detect 511 keV Photons With (in order of importance): >85% efficiency <5 mm spatial resolution “low” cost (<$100 / cm 2 ) “low” dead time (<1 µs cm 2 ) <5 ns fwhm timing resolution <100 keV fwhm energy resolution Based on Current PET Detector Modules

28. Synergies... Scintillators Photodetectors Electronics Computation

29. Very Strong Parallels... New Scintillators Developed Recently Image courtesy of E. Auffray, CERN LSO PbWO 4 Image courtesy of C. Melcher, CTI PET Systems Discovered in ~1992. Approximately 10 years of R&D before large scale production. Development efforts driven by end users, but included efforts of luminescence scientists, spectroscopists, defects scientists, materials scientists, and crystal growers.

30. Scintillator Properties Different Tradeoffs Required PbWO 4 Lu 2 SiO 5 Density (g/cc): 8.37.4 Attenuation Length (cm):0.91.2 Light Output (phot/MeV):20025,000 Decay Time (ns):1040 Emission Wavelength (nm):420420 Radiation Hardness (Mrad):>1010 Dopants:Y, NdCe Cost per cc:$1>$25

31. Avalanche Photodiode Arrays RMD, Inc. Hamamatsu Photonics Advantages: High Quantum Efficiency  Energy Resolution Smaller Pixels  Spatial Resolution Individual Coupling  Spatial Resolution Challenges: Dead Area Around Perimeter Signal to Noise Ratio Reliability and Cost

32. APD Requirements CalorimetryPET High Gain?:YesYes High QE / Blue Sensitivity?:YesYes Radiation Hardness?:YesNo Nuclear Counter Effect?:YesNo Timing Signal (low C)?: NoYes High Packing Density?:NoYes Sensitive to Leakage Current?:~Yes Different Tradeoffs Required

33. Electronics Requirements CalorimetryPET Low Noise Analog Amplifier?:YesYes Low Power Consumption?:YesYes Mixed-Mode Custom ICs?:YesYes Real-Time Data Correction?:YesYes Highly Parallel Readout?:YesYes High Data Rate?:YesYes Many Similarities

34. Electronics Requirements CalorimetryPET Radiation Damage?:YesNo Analog Dynamic Range:HighLow Self-Generated Timing Signal?:NoYes Asynchronous Inputs?:NoYes Event Size / Complexity?: HighLow Multiple Trigger Levels?:YesNo “Good” Event Rate?:kHzMHz Different Tradeoffs Required

35. Computation Requirements CalorimetryPET Significant Computation?:YesYes Monte Carlo Simulation?:YesYes Large Programming Project?:YesYes Complexity of Analysis?:HighLow Data Set Size?: TB–PBGB Time to Finish Analysis?:YearsMinutes FDA Certification Required?:NoYes Different Tradeoffs Required

36. Final Thoughts Many Synergies Exist Between HEP & PET Scintillators, detectors, electronics, computing, … Tools & experience are particularly valuable PET is a Mature, Commercial Technology  Innovations will only be used if they are clearly superior (not just novel)  All requirements must be met  Cost is very important Difficult to Transfer Identical Technology Need to optimize for PET tradeoffs