1. Special Applications for Scintillating Crystals in Medical Imaging Craig Woody Brookhaven National Lab SCINT 2007 Wake Forest University June 7, 2007

2. Using Nuclear Medicine to Help Solve Problems in Today’s Society n Drug Addiction n Nicotine Addiction n Alcoholism n Attention Deficit Disorders n Obesity These diseases are all related to the dopamine neurotransmitter system in the brain and can be studied using Positron Emission Tomography C.Woody, SCINT 07, 6/7/07 2

3. C.Woody, SCINT 07, 6/7/073 The Dopamine System in the Brain DA MAO A DA signal DA 11 C-Cocaine All drugs which are abused by humans increase the dopamine levels in the brain Striata

4. C.Woody, SCINT 07, 6/7/074 New Medical Imaging Detectors Being Developed at BNL RatCAP new tomograph for brain imaging of unanaesthetized rats using PET Wrist Detector non-invasive measurement of blood input function for human PET studies Simultaneous PET and MRI small animal or breast imager based on a non-magnetic version of the RatCAP Beta Microprobe Anger PET Camera

5. C.Woody, SCINT 07, 6/7/075 Imaging Awake Animals 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 often wants to use PET to study neurophysiological activity and behavior in laboratory animals in order to better understand these effects in humans.

6. C.Woody, SCINT 07, 6/7/076 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

7. C.Woody, SCINT 07, 6/7/077 Tomograph Ring Readout chip APD LSO Socket 4x8 array of LSO crystals (2x2x5 mm 3 ) 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

8. C.Woody, SCINT 07, 6/7/078 Crystal Arrays LSO Minimize size and weight High stopping power Fast timing for coincidence measurements Chose 2.2 x 2.2 x 5 mm 3 crystals to match to Hamamatsu S8550 APDs Gamma ray efficiency @ 511 keV ~ 41% Overall sensitivity of the RatCAP ~0.5% (comparable to other small animal PET scanners) Background from 176 Lu decay gives ~ 2600 dps for whole system (true coincidence rate ~ 80 cps)

9. C.Woody, SCINT 07, 6/7/079 Optimization of Light Collection Ray Tracing Best light yield was found to be with no optical coupling between crystals and reflectors and silicon cookie between crystals and APD Maximize photoelectron yield  LSO  25,000  /MeV  light collection ~ 0.6  area matching to APD = 0.53  APD QE ~ 70% Average p.e. yield ~ 5400 p.e./MeV  ~ 15% (2.7 max/min) over 384 pixels   ~ 8.5% (2.0 max/min) with gain matching of APDs

10. C.Woody, SCINT 07, 6/7/0710 Production of Crystal Arrays Cutting, polishing and assembly process Produced by Proteus/Agile Engineering Slabs cut and stacked with reflector between layers without glue (no optical coupling on sides) Layers are cut and stacked to form pixel arrays Glued to a reflector on a thin glass plate on one end (opposite readout)

11. C.Woody, SCINT 07, 6/7/0711 Readout Electronics Totally Digital Output 5 bit address Leading edge gives timing No ADC’s Minimizes cabling ZCD Bare chip (1 st prototype) Packaged chip Custom ASIC ( 0.18  m CMOS) 32 ch. preamp, shaper, disc. ~ 1W total power New chip VGA Improved timing Energy window LVDS interface 4.5 x 3.3 mm

12. C.Woody, SCINT 07, 6/7/0712 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

13. C.Woody, SCINT 07, 6/7/0713 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

14. C.Woody, SCINT 07, 6/7/0714 Animal Training

15. C.Woody, SCINT 07, 6/7/0715 Mounting the RatCAP to the Head

16. C.Woody, SCINT 07, 6/7/0716 Wearing the RatCAP Rat during awake image acquisition

17. C.Woody, SCINT 07, 6/7/0717 RatCAP Version 2 Redesigned ASIC, flex circuit, TSPM and DAQ Larger aperture (40 mm) Accommodates larger crystals (5  7 mm) for improved sensitivity ( ~ x2) Integrated cooling Non-magnetic Improved mounting system to rat’s head New design features RatCAP II

18. C.Woody, SCINT 07, 6/7/0718 Images with RatCAP II TransverseCoronalSaggital 11 C-Raclopride (ex vivo) TransverseCoronal Saggital FDG Awake

19. C.Woody, SCINT 07, 6/7/0719 Wrist Scanner for Measuring Radioactivity in the Blood Studies of dynamical processes with PET requires measuring the tracer concentration in the blood as a function of time. RatCAP modules

20. C.Woody, SCINT 07, 6/7/0720 Imaging the Wrist Artery MicroPET R4Wrist Scanner ArteryVein 1 cm Human Wrist

21. C.Woody, SCINT 07, 6/7/0721 Simultaneous PET/MRI Compared with PET/CT Images are perfectly co-registered Less radiation dose (~ ½ of PET/CT) MRI provides better soft tissue contrast PET imageMRI Image Simultaneous PET/MRI imaging provides high resolution anatomical data from MRI along with functional information from PET

22. C.Woody, SCINT 07, 6/7/0722 PET/MRI Based on the RatCAP Design A non-magnetic version of the RatCAP detector is inserted into an existing MRI scanner and PET and MRI images are obtained simultaneously RatCAP detectors and electronics Used with anesthetized rats

23. C.Woody, SCINT 07, 6/7/0723 Simultaneous PET-MRI Rat Brain Images MRI PET Overlay RatCAP I

24. C.Woody, SCINT 07, 6/7/0724 Simultaneous PET-MRI Images with RatCAP II MRI PET Overlay Striatum phantom

25. C.Woody, SCINT 07, 6/7/0725 Beta Microprobe LSO crystal attached to an optical fiber and read out with a PMT Positrons in PET have energies of a few hundred keV ( range ~ several mm in blood or tissue ) Can be detected directly using plastic or crystal scintillators

26. C.Woody, SCINT 07, 6/7/0726 Comparison of LSO vs Plastic Scintillator Response of LSO and plastic scintillation probes to betas ( 32 P) and gamma rays ( 137 Cs). Range and energy loss of positrons in LSO and plastic scintillator

27. C.Woody, SCINT 07, 6/7/0727 Input Function Measured with Microprobe LSO microprobe (0.3 mm dia. x 0.5 mm) inserted inside an 18 gauge syringe needle Input function measured in the tail vein of a rat ++ Region of sensitivity around the probe can be selected by adjusting the readout threshold to improve spatial resolution

28. C.Woody, SCINT 07, 6/7/0728 Rat Brain Studies with Microprobe Uptake of 11 C-methylphenidate in the nucleus accumbens region of a rat brain with an LSO probe nucleus accumbens ~ 2 mm

29. C.Woody, SCINT 07, 6/7/0729 Anger PET Camera P.Vaska BNL Medical Dept. Goal: ~1 mm FWHM spatial resolution Concept: Use Anger camera technique LSO and APDs Photosensor on both sides for DOI (no lightguide necessary) Advantages over current small-crystal designs Higher sensitivity - no gaps Scalable to higher resolution - thickness determines resolution Stackable to increase sensitivity Lower cost vs. APD LSO slab 

30. C.Woody, SCINT 07, 6/7/0730 Possible Application to Small Animal Imaging 6 cm dia boules of LSO  Annulus detector with no edge effects Depth of interaction from two layer readout Whole body mouse scanner 1 mm spatial resolution would be very advantageous in imaging mice LSO

31. C.Woody, SCINT 07, 6/7/0731 Summary New scintillating crystals such as LSO have opened up many new and exciting possibilities for medical imaging Applications of PET to both human and animal studies has greatly improved our ability to diagnose and treat many types of diseases The prospect for new even brighter and faster scintillators holds great promise for making further advances in nuclear medicine and improved health care

32. C.Woody, SCINT 07, 6/7/0732 The Team P. Vaska, D.Schlyer, C. Woody, J.-F. Pratte, S. Junnarkar, J.Fried, P. O’Connor, V. Radeka, S. Stoll, M. Purschke, W.Lenz, S.-J. Park, S. Southekal, A. Kriplani, S. Krishnamoorthy, S. Maramraju, D.Tomasi, S.Solis-Najera, S.D.Smith, W.Rooney, D.Schulz, D.Lee, W. Schiffer, V.Patel, S.Dewey, F.Henn, J.Neill, D.Kaluhiokalani, R.Lecomte, R.Fontaine RatCAP Group BNL MRI Group