1. The RatCAP Conscious Small Animal PET Tomograph

2. 2 Imaging The Awake Animal Animals need to be anesthetized during PET imaging due to their inability to lie motionless in the scanner Anesthesia can greatly depress brain functions and affect the neurochemistry that one is trying to study Cannot study animal behavior while under anesthesia One wants to study neurophysiological activity and behavior in laboratory animals using PET in order to better understand these effects in humans.

3. 3 RatCAP: Rat Conscious Animal PET A miniature, complete full-ring tomograph mounted to the head of an awake rat. Compact, light weight (< 200 g), low power detector Small field of view (38 mm dia. x 18 mm axial) Attached to the head of the rat and supported by a tether which allows reasonable freedom of movement for the animal

4. 4 Tomograph Ring LSO array Ring containing 12 block detectors of 2x2 mm 2 x 5 mm deep LSO crystals with APDs and integrated readout electronics APD (Hamamastu S8550) Actual RatCAP Ring RatCAP II

5. 5 LSO Crystal Arrays Studying different types of crystal arrays to optimize light output and energy resolution CTI white powder reflector Proteus unbonded 3M reflector Proteus single crystals

6. 6 Light Output and Uniformity of Crystal Arrays Proteus cutting, polishing and assembly process Average light yield ~ 5400 p.e./MeV with APD (average APD QE ~ 0.7) Spread of average from array to array  ~ 5 % Average spread within an array  ~ 18% Total spread within an array up to ± 50 %

7. 7 Light Ouput Variation for All RatCAP Crystals

8. 8 Optimization of Light Collection unwrapped air unwrapped cookie wrapped cookie wrapped air Dashed = Measured Solid = Opticad OPTICAD Ray Tracing Program 2x2 mm 2 single crystals wrapped in 3M reflector and coupled with a silicone cookie to a calibrated PMT N pe /MeV = N  /MeV x  x QE 2400 = 25,000 x 0.4 x 0.24

9. 9 Avalanche Photodiodes 4x8 array 1.6 x 1.6 mm 2 active pixel area Hamamatsu S8550 N pe ~ 2700 Typical G ~ 50  ~ 135K signal e’s Common voltage for each 16 channels Dark current < 40 nA (~ 1.2 nA/ch) Expected noise in final ASIC ~ 1100 e’s (C T ~ 10 pF) G ~ 50

10. 10 APD Gain and Quantum Efficiency Variation Measured with N 2 laser + optical fiber Gain + Quantum Efficiency variation Total spread ~ ± 20 % Channel to channel differences dominated by quantum efficiency variation

11. 11 Readout Electronics Totally Digital Output 5 bit address Leading edge gives timing No ADC’s Minimizes cabling ZCD Bare chip Packaged chip Custom ASIC ( 0.18  m CMOS) 32 channels preamp, shaper, discriminator ~ 1W total power

12. 12 New ASIC Built in ESD protection Programmable gain allows equalization of photopeak signals into zero crossing discriminator to minimize time dispersion Dual level discriminator for triggering (  E energy window) Lower noise, better timing resolution Low Voltage Differential Signaling (LVDS) - minimizes digital noise pick up by sensitive analog circuitry 40 new chips delivered in Nov ’06 177 more chips possible from remaining wafers 3.3 mm 4.5 mm J-F. Pratte

13. 13 ASIC Dynamic Range 33 33 Max (25 fC)Min(8.6 fC) 2.62 ns RMS (6.2 ns fwhm) Measured with laser Max Avg Min J.-F. Pratte, A.Villeneuva B. Yu Light spread within pixels determines dynamic range needed Adjust gain of each half-APD to put 3  of maximum pixel at top of range

14. 14 PET/MRI Data Acquisition System Need to keep computers, power supplies, cooling fans, etc all outside fringe field of MRI ASIC Scanner Timestamp and Signal Processing Module (TSPM) G-link transmit G-link receive G-link transmit Address Decoder Time Stamp ASIC programming G-link receive G-link transmit G-link receive PCI Interface Card Ring Controller Data Repackaging PCI Bus Interface PCI Automatic Calibration Readout And Test (PACRAT) Software Optical Link Electronics, interface cards and software were all developed at BNL

15. 15 Energy and Time Resolution Differential pulse height spectrum Threshold scan Threshold (mV) FWHM ~ 23% Thresh 2  ~28 ns Results with version 1 of the chip New chip gives 18.7% energy resolution and 6.6 ns timing resolution, and has variable gain for each channel for better energy matching Average threshold ~ 146 keV

16. 16 Position Resolution Rat Brain Striatum Phantom FWHM (mm) R4 MicroPET RatCAP 7 mm 15 mm Point Source Resolution Intrinsic Spatial Resolution 1.28 mm FWHM Concorde P4 MicroPET = 1.75 mm UCLA MicroPET = 1.58 mm 3.4:1 activity ratio (striatum to background)

17. 17 Sensitivity RatCAP Point Source Sensitivities 0.7% @ 150 kev 0.4% @ 400 keV Small Animal PET Sensitivities (Threshold = 250 keV) microPET (original) 0.56% ATLAS 1.8% microPET R4 4.4% microPET P4 2.3% microPET II (proto)2.3% microPET Focus 220 3.4% microPET Focus 120 7.7% microPET R4 = 45 kcps @ 6 uCi/cc Count Rate (kcps) 4  Ci 2  = 40 ns

18. 18 RatCAP Support System Weight is completely counterbalanced (animal feels only inertia) Gimbal ring allows head movement Inner ring attaches to head which mounts to tomograph

19. 19 Methamphetamine Images Using the RatCAP RatCAP The resolution of the RatCAP is slightly better than the commercial MicroPET scanner MicroPET RatCAP vs MicroPET Time Activity Curve 0 50 100 150 200 250 0100200300400500600700 Time in seconds ROI Activity in nCi/cc RatCAP MicroPET

20. 20 Fluoride Scan 3 mCi 18 F Injection Uptake mainly in the bone Brain Skull Artifact ( due to randoms correction)

21. 21 Images With RatCAP II TransverseCoronalSaggital 11 C-Raclopride (ex vivo) TransverseCoronal Saggital FDG Awake

22. 22 Summary The ability to image the awake animal will open up many new possibilities in neurophysiology and neurochemistry The RatCAP is a fully functional miniature 3D tomograph that can be used for PET imaging of live, unanesthesized rats, and will provide one of the first opportunities to perform detailed studies on awake animals The device can also be used as a standard small animal tomograph for anesthesized animals, and can be used for other applications using the same detector components The first preliminary studies using the RatCAP have been completed, and we are now looking forward to the first real awake animal images and to improving its design in the future.

23. 23 The Team P. Vaska, C. Woody, D. Schlyer, J.-F. Pratte, P. O’Connor, V. Radeka, S. Shokouhi, S. Stoll, S. Junnarkar, M. Purschke, S.-J. Park, S. Southekal, V. Dzhordzhadze, W. Schiffer, D. Marsteller, D. Lee, S.Dewey, A. Villanueva, S. Boose, A. Kandasamy, B. Yu, A. Kriplani, S. Krishnamoorthy, S. Maramraju Brookhaven National Laboratory J. Neill, M. Murphy, T. Aubele, R. Kristiansen Long Island University R. Lecomte and R. Fontaine University of Sherbrooke