Positron Emission Tomography Oct. 28, 2003

Chang Kim, GE Medical Systems

1. Anatomic vs. Functional Imaging2. Anatomy of PET

• What is PET? • Isotopes and Detector

3. Basic physics and Principles4. Detector example

* Most of Presentations are from GE internal contributions.

Anatomic vs. Functional ImagingAnatomic vs. Functional Imaging

Anatomic ImagingAnatomic Imaging– Physical Structures, Bulk Properties of PatientPhysical Structures, Bulk Properties of Patient

– Generally Very High Resolution Images (~1mm or less)Generally Very High Resolution Images (~1mm or less)

– X-Ray/CT, MRI, UltrasoundX-Ray/CT, MRI, Ultrasound

Functional ImagingFunctional Imaging– Biochemical ProcessesBiochemical Processes Ongoing in Patient Ongoing in Patient

– Generally Poorer Resolution (~4-5mm or more)Generally Poorer Resolution (~4-5mm or more)

– Radioisotope Techniques: NM /SPECT, PETRadioisotope Techniques: NM /SPECT, PET

– Other Techniques: MR (MRS, fMRI), MEG (MSI), ...Other Techniques: MR (MRS, fMRI), MEG (MSI), ...

MR Scan (or CT)MR Scan (or CT)

Anatomic imaging

Functional imaging

Glucose + Isotope (e+)

Injection(~2-5mCi)

Scan (15-30 minutes)

Tools for • Initial diagnosis • Progress or success evaluationafter chemotherapy & operation

What is PET?What is PET?

• Isotope production CYCLOTRONS

• Tracer production CHEMISTRY SYSTEMS

• Imaging SCANNER

Anatomy of PET

Positron Emitting IsotopesPositron Emitting IsotopesIsotope Half-Life Production

Carbon-11 20.5 min 14N(p,)11C

Nitrogen-13 10.0 min 16O(p,13N

Oxygen-15 2.1 min 14N(d,n)15O

Fluorine-18 110 min 18O(p,n)18F (F-)

20Ne(d,)18F (F2)

Gallium-68 68 min Daughter of Ge-68 (271days)

Rubidium-82 1.27 min Daughter 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: 18F FDG ( 18F labeled fluorodeoxyglucose )

Tracer binds to Tracer binds to receptors expressed on receptors expressed on one tumor type, not one tumor type, not the other.the other.

Prolactinoma is often Prolactinoma is often responsive to responsive to chemotherapy, chemotherapy, avoiding surgery for avoiding surgery for patient.patient.

Differentiating Tumor Types with PETDifferentiating Tumor Types with PET

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 PETMonitoring Therapy with PET

Basic Physics

~1-3mm511KeV

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

Coincidence DetectionCoincidence Detection

DET 1 DET 2

Pulse Processing

AND

Pulse Processing

• Events occurring anywhere on line between detectors Events occurring anywhere on line between detectors contribute coincidence counts to detector pair.contribute coincidence counts to detector pair.

• Recorded counts are proportional to line integral of Recorded counts are proportional to line integral of activity between the detectors.activity between the detectors.

Basic Principles

Projection Data CollectionProjection Data Collection

PMT

PMT

COINCIDENCE PROCESSING

DETECTOR RING

ProcessingElectronics

ProcessingElectronics

CoincidenceProcessor

Data Sorting,Histogram

Image ReconComputer Images

Basic Principles

Coincidence EventsCoincidence 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

1-to-1 CouplingExcellent livetime characteristics, but expensive, and limited in size to smallest available PMT (~1cm2).

Block DetectorIndividual crystals “pipe” light to detectors.

More complex, but required with low light output--BGO.

Anger CameraLight 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 AssembliesDetector Assemblies

PMT

A B

No Optical grease

(a) (b)

(c) (d) Alignment

Detector example Light sharing Decoding x = A/(A+B)

Two Dimensional extension….

BGO NaI(Tl) GSO LSO

PRODUCE

LIGHT

(cm-1) 0.95 0.37 0.67 0.89

Photofraction ~40% ~15% ~35% ~30%

Light Output 20-25 100 35 75

Decay Constant 300 230 65 50

Radioactive NO NO NO YES

Melting Point 1050 - >2000 >2000

Furnace Platinum Iridium Iridium

Cost $10/cc $5/cc $20/cc >$25/cc

Detector MaterialsDetector Materials

STOP

PHOTONS

GROW

CRYSTALS

Many new crystals from IEEE 2003…

Detector RequirementsDetector Requirements

Goal Requirement

High Spatial Resolution Small Detector Elements High Photofraction

High Sensitivity High Stopping Power

Low Scatter Fraction Good Energy Resolution

Low Randoms Good Timing Resolution

Low Deadtime Fast Event Handling (High Livetime) Small Channel Size Limited Multiplexing

Low Cost None of the Above

PET Image

My Objective New and better detector design using GEANT4 Better information to Physicians Better patient care and treatment

Clinical PET ApplicationsClinical PET ApplicationsApplications

• Cardiology Cardiomyopathy or disease of the myocardium, etc. Flow tracer: NH3, 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.

http://www.indyrad.iupui.edu/IUPET/• Has a outline of PET applicationsHas a outline of PET applications

http://pet.radiology.uiowa.edu• Lots of pictures, simple explanations of PETLots of pictures, simple explanations of PET

http://faculty.washington.edu/chudler/introb.html• Nice description of brain anatomy, function, methods Nice description of brain anatomy, function, methods

and disease researchand disease research http://www.bic.mni.mcgill.ca

• Many examples and animationsMany examples and animations

Megazines : Medical Imaging, Radiology today, Megazines : Medical Imaging, Radiology today, Diagnostics ImagingDiagnostics Imaging

http://www.indyrad.iupui.edu/IUPET/• Has a outline of PET applicationsHas a outline of PET applications

http://pet.radiology.uiowa.edu• Lots of pictures, simple explanations of PETLots of pictures, simple explanations of PET

http://faculty.washington.edu/chudler/introb.html• Nice description of brain anatomy, function, methods Nice description of brain anatomy, function, methods

and disease researchand disease research http://www.bic.mni.mcgill.ca

• Many examples and animationsMany examples and animations

Megazines : Medical Imaging, Radiology today, Megazines : Medical Imaging, Radiology today, Diagnostics ImagingDiagnostics Imaging

More info on the WEB and others…More info on the WEB and others…

Intra-pulmonary lesionPET-CT fusion localizes

PET-CT

April 2001 JNM, 11N-12N (2pp)April 2001 JNM, 11N-12N (2pp)CAG-00065 HCFA report (80pp)CAG-00065 HCFA report (80pp)www.hcfa.gov/pubforms/06_cim/ci50.htmwww.hcfa.gov/pubforms/06_cim/ci50.htm

April 2001 JNM, 11N-12N (2pp)April 2001 JNM, 11N-12N (2pp)CAG-00065 HCFA report (80pp)CAG-00065 HCFA report (80pp)www.hcfa.gov/pubforms/06_cim/ci50.htmwww.hcfa.gov/pubforms/06_cim/ci50.htm

1994– FDA approves FDG for abnormal

glucose metabolism for foci of epileptic seizures

1995 (1)– Rb82 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)– Rb82 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 PET reimbursement

Reimbursement and Regulatory issues..Reimbursement and Regulatory issues.. Dec 1, 2001 (Medicare): 82Rb 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

Glucose & Methionine for CharacterizationGlucose & 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