2. Positron Emission Tomography Oct. 28, 2003 Chang Kim, GE Medical Systems 1.Anatomic vs. Functional Imaging 2.Anatomy of PET What is PET? Isotopes and Detector 3.Basic physics and Principles 4.Detector example * Most of Presentations are from GE internal contributions.

3. Anatomic vs. Functional Imaging Anatomic Imaging Anatomic Imaging –Physical Structures, Bulk Properties of Patient –Generally Very High Resolution Images (~1mm or less) –X-Ray/CT, MRI, Ultrasound Functional Imaging Functional Imaging –Biochemical Processes Ongoing in Patient –Generally Poorer Resolution (~4-5mm or more) –Radioisotope Techniques: NM /SPECT, PET –Other Techniques: MR (MRS, fMRI), MEG (MSI),...

4. MR Scan (or CT) Anatomic imaging

5. Functional imaging Glucose + Isotope (e+) Injection(~2-5mCi) Scan (15-30 minutes) Tools for Initial diagnosis Progress or success evaluation after chemotherapy & operation

6. What is PET? Isotope production CYCLOTRONS Tracer production CHEMISTRY SYSTEMS Imaging SCANNER Anatomy of PET

7. Positron Emitting Isotopes IsotopeHalf-LifeProduction Carbon-1120.5 min 14 N(p,  ) 11 C Nitrogen-1310.0 min 16 O(p,  13 N Oxygen-15 2.1 min 14 N(d,n) 15 O Fluorine-18110 min 18 O(p,n) 18 F (F - ) 20 Ne(d,  ) 18 F (F 2 ) Gallium-6868 minDaughter of Ge-68 (271days) Rubidium-82 1.27 minDaughter of Sr-82 (25days) Small elements (C,N,O,F) allow “real” biochemistry Short half-lives make tracer production an integral part of PET  Tracer  ex: 18 F FDG ( 18 F labeled fluorodeoxyglucose )

8. Tracer binds to receptors expressed on one tumor type, not the other. Tracer binds to receptors expressed on one tumor type, not the other. Prolactinoma is often responsive to chemotherapy, avoiding surgery for patient. Prolactinoma is often responsive to chemotherapy, avoiding surgery for patient. Differentiating Tumor Types with PET

9. Effects of therapy on tumor metabolism seen in hours. Effects of therapy on tumor metabolism seen in hours. Anatomic change (size reduction) will take weeks. Anatomic change (size reduction) will take weeks. Monitoring Therapy with PET

10. Basic Physics   ~1-3mm 511KeV Positron travels 1-3 mm before annihilation (depending on energy) Energy and Momentum conservation - 511 keV Photons and back-to-back Simultaneous detection of two 511KeV photons  - event along line between detectors

11. Coincidence Detection DET 1 DET 2 Pulse Processing AND Pulse Processing Events occurring anywhere on line between detectors contribute coincidence counts to detector pair.Events occurring anywhere on line between detectors contribute coincidence counts to detector pair. Recorded counts are proportional to line integral of activity between the detectors.Recorded counts are proportional to line integral of activity between the detectors. Basic Principles

12. Projection Data Collection R PMT COINCIDENCE PROCESSING DETECTOR RING Processing Electronics Processing Electronics Coincidence Processor Data Sorting, Histogram Image Recon Computer Images Basic Principles

13. Coincidence Events 1 1. Detected True Coincidence Event 2 2. True Event Lost to Sensitivity or Deadtime 3 3. True Event Lost to Photon Attenuation 4 4. Scattered Coincidence Event 5a 5b 5a,b. Random Coincidence Event

14. 1-to-1 Coupling Excellent livetime characteristics, but expensive, and limited in size to smallest available PMT (~1cm 2 ). Block Detector Individual crystals “pipe” light to detectors. More complex, but required with low light output--BGO. Anger Camera Light from scintillator is distributed among several PMT’s; measured distribution determines location. Poor livetime, but can have good resolution with enough light output--NaI(Tl). Detector Assemblies

15. PMT A B No Optical grease (a) (b) (c) (d) Alignment Detector example Light sharing  Decoding x = A/(A+B)

16. Two Dimensional extension….

18. BGONaI(Tl)GSOLSO PRODUCE LIGHT  (cm -1 )0.950.370.670.89 Photofraction~40%~15%~35%~30% Light Output 20-251003575 Decay Constant 3002306550 RadioactiveNONONOYES Melting Point1050->2000>2000 FurnacePlatinumIridiumIridium Cost $10/cc$5/cc$20/cc>$25/cc Detector Materials STOP PHOTONS GROW CRYSTALS Many new crystals from IEEE 2003…

19. Detector Requirements GoalRequirement High Spatial ResolutionSmall Detector Elements High Photofraction High SensitivityHigh Stopping Power Low Scatter FractionGood Energy Resolution Low RandomsGood Timing Resolution Low Deadtime Fast Event Handling (High Livetime) Small Channel Size Limited Multiplexing Low CostNone of the Above

20. PET Image My Objective  New and better detector design using GEANT4  Better information to Physicians  Better patient care and treatment

21. Clinical PET Applications Applications Cardiology  Cardiomyopathy or disease of the myocardium, etc.  Flow tracer: NH 3, Metabolic tracer: FDG Neurology  Alzheimer’s, Parkinson’s  Tumor recurrence and viability vs. post-surgical, post-chemo, post-radiotherapy changes of tissue necrosis Oncology Melanoma, Lymphoma, etc.

22. http://www.indyrad.iupui.edu/IUPET/ http://www.indyrad.iupui.edu/IUPET/ http://www.indyrad.iupui.edu/IUPET/ Has a outline of PET applications Has a outline of PET applications http://pet.radiology.uiowa.edu http://pet.radiology.uiowa.edu http://pet.radiology.uiowa.edu Lots of pictures, simple explanations of PET Lots of pictures, simple explanations of PET http://faculty.washington.edu/chudler/introb.html http://faculty.washington.edu/chudler/introb.html http://faculty.washington.edu/chudler/introb.html Nice description of brain anatomy, function, methods and disease research Nice description of brain anatomy, function, methods and disease research http://www.bic.mni.mcgill.ca http://www.bic.mni.mcgill.ca http://www.bic.mni.mcgill.ca Many examples and animations Many examples and animations  Megazines : Medical Imaging, Radiology today, Diagnostics Imaging http://www.indyrad.iupui.edu/IUPET/ http://www.indyrad.iupui.edu/IUPET/ http://www.indyrad.iupui.edu/IUPET/ Has a outline of PET applications Has a outline of PET applications http://pet.radiology.uiowa.edu http://pet.radiology.uiowa.edu http://pet.radiology.uiowa.edu Lots of pictures, simple explanations of PET Lots of pictures, simple explanations of PET http://faculty.washington.edu/chudler/introb.html http://faculty.washington.edu/chudler/introb.html http://faculty.washington.edu/chudler/introb.html Nice description of brain anatomy, function, methods and disease research Nice description of brain anatomy, function, methods and disease research http://www.bic.mni.mcgill.ca http://www.bic.mni.mcgill.ca http://www.bic.mni.mcgill.ca Many examples and animations Many examples and animations  Megazines : Medical Imaging, Radiology today, Diagnostics Imaging More info on the WEB and others…

23. Intra-pulmonary lesion PET-CT fusion localizes PET-CT

24. April 2001 JNM, 11N-12N (2pp) CAG-00065 HCFA report (80pp) www.hcfa.gov/pubforms/06_cim/ci50.htm April 2001 JNM, 11N-12N (2pp) CAG-00065 HCFA report (80pp) www.hcfa.gov/pubforms/06_cim/ci50.htm 1994 –FDA approves FDG for abnormal glucose metabolism for foci of epileptic seizures 1995 (1) –Rb 82 chloride myocardial perfusion with inconclusive SPECT or w/o SPECT 1997 –FDA Modernization and Accountability Act (FDAMA) –Congress mandated FDA to provide a mechanism for PET approval of PET radiopharmaceuticals January 1998 (2) –FDA approval for FDG –indeterminate solitary pulmonary nodule –initial staging of non–small cell lung cardinoma 1994 –FDA approves FDG for abnormal glucose metabolism for foci of epileptic seizures 1995 (1) –Rb 82 chloride myocardial perfusion with inconclusive SPECT or w/o SPECT 1997 –FDA Modernization and Accountability Act (FDAMA) –Congress mandated FDA to provide a mechanism for PET approval of PET radiopharmaceuticals January 1998 (2) –FDA approval for FDG –indeterminate solitary pulmonary nodule –initial staging of non–small cell lung cardinoma July 1999 (3) –colorectal cancer with rising carcinoembryonic antigen (CEA) –Detection of recurrent melanoma –staging and restaging of Hodgkin’s and non-Hodgkin’s lymphoma July 1, 2001 (8) –non–small cell lung cancer –esophageal cancer –colorectal cancer –Lymphoma –Melanoma –head and neck cancers, excluding central nervous system and thyroid cancers –Myocardial Viability –Refractory Seizures July 1999 (3) –colorectal cancer with rising carcinoembryonic antigen (CEA) –Detection of recurrent melanoma –staging and restaging of Hodgkin’s and non-Hodgkin’s lymphoma July 1, 2001 (8) –non–small cell lung cancer –esophageal cancer –colorectal cancer –Lymphoma –Melanoma –head and neck cancers, excluding central nervous system and thyroid cancers –Myocardial Viability –Refractory Seizures PET reimbursement

25. Reimbursement and Regulatory issues.. Dec 1, 2001 (Medicare): 82 Rb scan : $953 FDG scan : $1375 ( $2331 for 2000) But, for gamma camera with at least one inch thick crystal or FDA 510(k) clearance ( ongoing issues ) Not for screening Diagnosis : to avoid an invasive diagnostic procedure or to determine the optimal anatomical location for an invasive diagnostic procedure Staging and Restaging : the stage of the cancer remains in doubt after standard diagnostic workup; Restaging after treatment ( expect to replace one or more conventional imaging studies ) Not for monitoring during the planned course of therapy

26. Glucose & Methionine for Characterization Lesion which requires clarification in MR... Still not clear when looking with FDG... (due to brain metabolic activity) Actively growing without a doubt when tracked with methionine... Structure Energy Metabolism Growth Activity … depending on Cancer Type