1. From Novel g-2 Fast Calorimetry to a Superior PET Scanner Bill Worstell Chief Technology Officer PhotoDetection Systems, Inc.

2. Talk Overview What PET/CT is and why it is important –Brief Summary of Clinical Context The PDS PET/CT and its connection with Experimental High-Energy Physics –Detector Design + Implementation –Data Analysis/Processing + Image Algorithms The Future of PET/CT –Molecular Imaging + Molecular Medicine

3. PET Physics Measure positions and energies of coincident particles which generate triggers – sound familiar?

4. FDG-PET All of clinical PET is currently FDG-PET FDG developed at Brookhaven National Laboratory Nearly all tumors are FDG-avid

5. Clinical Applications of PET in Oncology Diagnosis Biopsy guidance Staging Radiation Therapy Planning Monitoring Response to Therapy Monitoring for Recurrence

6. Monitoring Response to Targeted Therapy

7. PET/CT Hybrid Scanners

8. Anatomical plus Functional Imaging -> Fusion Imaging CT Image gives anatomy PET Image gives function (-> in-vivo Quantitative Biochemistry)

9. PET is now a $1B/year business, Up from ~$10M/year in 1998 PET/CT was first commercially introduced in 2002, and now makes Up nearly 100% of the PET market

10. Distinguishing Features of PDS PET component of PET/CT Highest Sensitivity available Largest bore available (only 90cm PET/CT) Matches highest clinical spatial resolution available Lowest cost to manufacture Simple interfaces to alternative multislice CTs

11. Largest Bore PET/CT available Patient Bore (cm) PDS Resolve 9090 GE Discovery ST70 CTI/Siemens pico-3D70 CTI/Siemens Hi-Res70 Philips Gemini63 Manufacturer/Model Large-bore CTs have been introduced to satisfy the needs of radiation therapy planning applications – there is as yet no comparably large-bore PET/CT.

12. Highest Sensitivity PET/CT system Double the axial field of other scanners (32cm vs 16cm) –Larger coverage –Larger acceptance High stopping power Clinical applications: –Lower injected dose –Emerging radiotracers length

13. Highest PET/CT Image Quality Meets or exceeds the performance of competitive systems as quantified by NEMA standard tests and direct imaging comparisons CTI: Low resolution GE: Non-uniform intensity PDS: High resolution and uniform intensity PDS PET/CT 6.35 2.38 3.18 3.97 4.76 5.56 CTI Hi-Res

14. BU Physics Prototype Work Antecedent work: Muon g-2 fiber calorimeter prototypes SSC fiber calorimeter prototypes BU wavelength- shifting fiber PET prototypes –Patent filed 1995 –Photonics Center spin- off start-up 2000

15. Principle of Wavelength-Shifting Fiber Optic PET Readout Wavelength-shifting fiber readout technology familiar and proven by tile calorimeter groups for many years. Combination with Anger Logic readout is cost- effective and robust at high event rates. 1. Gamma ray enters crystal from positron annihilation 2. Interaction in crystal releases blue photons 3. Fiber absorbs blue photons and fluoresces green 4. Fibers carry green light to sensors 5. Other photons pass through mixer to photomultiplier tube

16. Commercial embodiment of WLS fiber readout 44 field-replaceable optics modules 11 field-replaceable electronics modules 11 parallel readout commercial PCs

17. PDS/Analogic PET/CT Prototype

18. Key to High Sensitivity and Low Cost: CsI(Na) Scintillator CsI(Na) developed at Kharkhov in collaboration with Budker Instititute in Novosibirsk Much lower cost to manufacture than alternatives –Low melting point –Low cost raw materials But slower decay

19. Accurate High-Throughput Data Acquisition and Signal Processing Fully digital, including digital triggering (unique to PDS) Digital waveform signal processing Fully buffered to eliminate downstream deadtime effects Cost-effective Programmable Logic Array Design

20. Key to High-throughput Data Processing: Parallel Readout Unique to PDS design Organizes lines-of- response into ordered pairs. Uniformly distributes data acquisition and data processing workload Built on a commercial off-the- shelf Linux cluster 2 3 4 5 6 7 8 9 10 11 1 3 masters

21. Optimal Use of Measured Data -- Diversity Signal Processing List mode event data packet: Weight each event by probability it is a True Mathematically optimal statistical treatment of diverse events Unique to PDS Randoms Trues + Scatters Total

22. Statistically principled fully-3D Maximum-Likelihood Image Reconstruction Factorized precalculated formulation unique to PDS Based on previously unnoticed symmetry Custom hardware parallel processing reconstruction accelerator

23. Continuous Bed Motion combined with fully-3D reconstruction Coordinate transformation to “virtual detector” which is co-moving with patient. PDS first to combine this with fully 3D reconstruction

24. The Future of PET/CT The Multi-slice CT revolution Radiation Therapy applications of PET/CT New and Emerging Radiotracers –Molecular Imaging and Molecular Medicine –Personalized Medicine

25. PET/CT and new Multi-slice CTs Customers are demanding top CT performance in PET/CTs, with Cardiac applications leading the way. (CT Angiography)

26. PET/CT and Radiation Therapy IMRT – Intensity Modulated Radiation Therapy directs beams with greater accuracy IGRT – Image Guided Radiation Therapy gives direction by imaging organs at delivery time FIGRT – Functional Image Guided Radiation Therapy on the near horizon

27. Emerging High- Specificity Radiotracers Ga-68 DOTATOC binds to somatostatin receptors overexpressed by neuroendocrine tumors

28. PET and Molecular Imaging

29. Things I Learned From Larry Love what you’re doing and let it show –It’ll make people want to join your team Talk fast, life is short –Assume your audience is quick on the uptake Put your best foot forward –No one else will do it for you Swing for the fences –Who knows how many at-bats you’ll get