Simulation Needs in PET Positron Emission Tomography ChinTu

Simulation Needs in PET (Positron Emission Tomography) Chin-Tu Chen, Ph. D. Department of Radiology & Committee on Medical Physics Pritzker School of Medicine & Division of Biological Sciences The University of Chicago

PET Principle P N + e+ + n + energy E = mc 2

Production of Isotopes (Mini-Cyclotron) 18 O (p, n) 18 F

PET Isotopes 15 O 13 N 11 C 18 F PET Tracers [15 O]-O 2 [15 O]-H 2 O 64 Cu 82 Rb 124 I [15 O]-H 2 O [15 O]-CO [13 N]-NH 3 [18 F]-FDOPA [13 N]-glutamate [18 F–] [11 C]-acetate [18 F]-FDG [11 C]-palmitate [11 C]-methionine

Metastatic Melanoma 71 -year-old male with metastatic melanoma on left shoulder discovered 12/94. CT performed on 7/10/95 demonstrated tumor of the distal femur with negative findings in the abdomen. Bone scan on 7/13/95 showed an abnormal femur and four spine lesions. Whole-body FDG PET scan demonstrates numerous lesions throughout the body. Patient was scheduled for an amputation and total knee replacement based on CT and bone scan results. After PET found multiple lesions, surgery was cancelled, avoiding both the cost and the trauma of an operation that would not be effective. Courtesy of Amjad Ali, M. D. • Rush-Presbyterian-St. Luke’s Medical Center

Alzheimer’s Disease

13 NH 3 Images

Clinical Applications of PET — In Cancer

PET/CT Imaging

Imaging of the Brain, Mind, Cognition, and Behavior

PET in Drug Development

Biochemical Imaging with Small Animals 11 CH 3 N O OCH 3 F [11 C]WIN 35, 428 micro. PET

micro. PET Images baby rhesus monkey brain phantom (25 cc) - 1. 2 m. Ci 18 FDG 1 hr. acquisition micro. PET EXACT HR+

Animal Studies: 11 C-WIN 35, 428 in collaboration with Bill Melega Vervet Monkey Transverse Coronal Rat Mouse x 2

FDG Whole Body Rat Study Injected dose: 2. 5 m. Ci Imaging time: ~2 hrs.

Mouse model with one tumor on each shoulder. The left tumor expresses the D 2 receptor gene and uptakes FESP, while the tumor on the right, represses the tk gene and uptakes FPCV.

Human PET: 3 -4 mm; Target: 1 -2 mm Animal PET: 1 -2 mm; Target: <0. 5 mm

Simulations in PET Source Distributions Imaging Physics Attenuation Scattering etc.

The neue Cologne Phantom 3 mm structure 2 mm structure

Simulations in PET Imaging System Geometry Configurations

HRRT: Octagon - 120, 000 crystals 936 electronic channels 4. 486*109 LORs

A Benchtop Prototype for High. Throughput Animal Imaging § HRRT modules • LSO crystals with DOI capability u good spatial resolution – ~2. 42 mm crystal pitch – ~10 mm DOI resolution u good detection sensitivity u high count rate • large detection sensitive area u ~25. 2 cm × 17. 4 cm u 72× 104 crystals per layer • off-shelf, well tested, costeffective design • adjustable energy and

Multi-Modality Integrative System PET/SPECT PET/MRI PET/SPECT/CT For Animal Imaging Siemens “Molecular Imaging”

Simulations in PET Photon Detection Scintillation Crystals Photon Sensors PMT/APD/Si. PM

Scintillation properties of primary crystals in PET Material Denstiy (g/cm 3) Decay time (ns) a. Light Yield Initial Photon Rate (ph/Me. V-ns) Energy resolution %@662 ke. V Na. I: Tl 3. 67 230 100 164 6. 5 Bi 4 Ge 3 O 12(BGO) 7. 13 300 22 27 9. 3 Gd 2 Si. O 5: Ce(GSO) 6. 71 60 27 167 7. 8 Y 2 Si. O 5: Ce(YSO) 4. 54 70 70 377 9. 0 Lu 2 Si. O 5: Ce(LSO) 7. 40 40 80 750 7. 9 c. Lu 7. 11 40 100 845 7. 5~9. 5 7. 40 40 61 575 12. 4 Lu 2 Si 2 O 7: Ce(LPS) 6. 23 38 70 692 9. 5~12. 5 Ba. F 2 4. 89 b 0. 8 27 b 2300 7~8 La. Br 3: Ce 0. 5% 5. 29 35 162 1743 3. 0 2(1 -x)Y 2 x. Si. O 5: Ce(LYSO) d. Lu 2(1 -x)Gd 2 x. Si. O 5: Ce(LGSO) a. Relative to Na. I(Tl)=100 is the fast scintillating component of Ba. F 2. cx=0. 1 dx=0. 1 b. It

PET Components F detectors – block detectors: BGO, LSO, GSO crystals

Quadrant Sharing Design 8 x 8 crystal matrix; two layer LSO-fast/LSO-slow (or LSO/GSO) F 128 single crystals in 2 layers 2. 1 x 7. 5 mm 3 F

Simulations in PET Electronics (Fast Electronic)

Custom Integrated Circuit Electronics Analog Detector Signals Detector Analog ASIC Processes Digital X, Y Energy, and Time Data Detector Digital ASIC Digital Coincidence ASIC Processes Digital Crystal Position and Time Data Processes Digital PET Coincidence Data

Serial Interface Gain Control DACs Preamps, Variable Gain Amps, Summers 6. 4 mm Constant Fraction Discriminator* ECL Driver CMOS PET Front End Integrated Circuit Gated Integrators CFD Thld DAC X, Y Offset DACs 6. 0 mm * U. S. Patent 5, 396, 187

Simulations in PET List Mode Position Energy Timing Depth-of-Interaction (DOI) Time-of-Flight (TOF)

DOI Detectors F Phoswich detectors LSO GSO/LSO PMT F photo-diodes scintillator (BGO) photo diode PMT

Depth-of-Interaction (DOI) Detector

Time-of-Flight Tomograph x D • Can localize source along line of flight - depends on timing resolution of detectors • Time of flight information can improve signal-to-noise in images - weighted backprojection along line-ofresponse (LOR) x = uncertainty in position along LOR = c. t/2 Karp, et al, UPenn

300 ps TOF Benefit of TOF Better image quality Faster scan time 5 Mcts TOF 1 Mcts TOF 5 Mcts 10 Mcts 5 Mcts 1 Mcts no TOF Karp, et al, UPenn

Simulations in PET Image Reconstruction Image Processing Image Analysis

Multi-Modality Bayesian Image Reconstruction Upper Two: 1. Co-registration of PET/SPECT with CT/MRI Filtered Back. Proj. 2. Incorporation of high-resolution information from the co 3. registered CT/MR images into a Bayesian image recons- Lower Two: 4. truction framework to enhance image quality of Multi-Modality PET/SPECT Image Reconstru. 3. Using the co-registered CT/MR images as an anatomic map Chen, Kao, et al

Dual Planar Detector High-Throughput Animal PET Imager Dual Layer D. O. I. Detectors (LSO) Variable Detector Face-to-Face Spacing

Example Reconstruction 25. 2 cm 5 cm ~16 cm Noiseless data Noisy data

Simulations in PET Physiology Biochemistry Biology

18 Fluoro-2 -deoxy-D-glucose

Simulations in PET System Geometry/Configuration Source Distribution/Physics Photon Detection/Collection Electronic List. Mode/DOI/TOF Image Reconstruction Physiological Modeling