positron emission tomography (revised)
TRANSCRIPT
Positron Emission Tomography Positron Emission Tomography (PET)(PET)
Created By: Hung VoCreated By: Hung Vo
Date: 11/02/2009Date: 11/02/2009
Course: Chem 717 - Instrumental Course: Chem 717 - Instrumental Analysis Analysis
Bringing the Invisible to LightBringing the Invisible to Light
What is Emission Tomography?What is Emission Tomography?
Human Illnesses and Behavioral Health. http://www.humanillnesses.com/images/hdc_0000_0001_0_img0004.jpg (accessed October 27, 2009).Epilepsy. http://www.epilepsinet.dk/images/pictures/spect-scanningstor.jpg (accessed October 27, 2009).Melissa Memorial Hospital. http://www.melissamemorial.org/userfiles/image/mri01.jpg (accessed Octoberr, 27, 2009).
SPECT MRIPET
Key steps in ET study Key steps in ET study
Radiopharmaceutical production:Radiopharmaceutical production: Create radiotracersCreate radiotracers
Administration of radiopharmaceutical:Administration of radiopharmaceutical: Injection, inhalationInjection, inhalation Higher amount = better qualityHigher amount = better quality Safety dose Safety dose
Data acquisition:Data acquisition: Imaging hardware record and detect Imaging hardware record and detect
gamma-raysgamma-rays Stored as projection measurements Stored as projection measurements
Image reconstruction:Image reconstruction: Filtered back projection (FBP) Filtered back projection (FBP)
creates tomographic images from creates tomographic images from projection dataprojection data
Image analysis:Image analysis: Image are analyzed for desired data Image are analyzed for desired data
or statisticsor statistics
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004. p14
RadiotracersRadiotracers
Unstable Unstable radioisotopesradioisotopes undergo radioactive decay undergo radioactive decay Nucleus is unstableNucleus is unstable Change in the number of Change in the number of
protons or neutrons to form a protons or neutrons to form a more stable configuration more stable configuration
For example: For example: 1818F-FDGF-FDG (Flourine-18-(Flourine-18-fluorodeoxyglucose)fluorodeoxyglucose) FDG is an analog of glucoseFDG is an analog of glucose 1818F is unstable radioisotopes F is unstable radioisotopes
that emits positronthat emits positron
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p24
Radioactive decayRadioactive decay
Alpha decay:Alpha decay:
Beta decay:Beta decay:
Positron decay:Positron decay:
Electron capture:Electron capture:
Isometric transitionIsometric transition
Saha, B. Basics of PET Imaging Physics, Chemistry, and Regulations. New York: Springer, 2005, p4
Annihilation ProcessAnnihilation Process
Saha, B. Basics of PET Imaging Physics, Chemistry, and Regulations. New York: Springer, 2005, p6
Positron comes to restPositron comes to rest Combine with an e- Combine with an e-
two photons (0.511 two photons (0.511 MeV) traveling in MeV) traveling in opposite direction opposite direction (~180(~180°°))
Gamma-ray region Gamma-ray region
General Mechanism of PET General Mechanism of PET ScannerScanner
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p16
What data is measured by the What data is measured by the Ring Detector in PET scanner?Ring Detector in PET scanner?
To measure To measure (x(xrr, Ф) , Ф) (sonogram)(sonogram)
PET measures sonogram PET measures sonogram by by electronic collimation electronic collimation
Coincidence eventCoincidence event Site of decay event is Site of decay event is
along the linealong the line
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p36
Scintillation DetectorsScintillation Detectors
ScintillatorScintillator convert high-energy photons into convert high-energy photons into low-energy photons (in visible region)low-energy photons (in visible region)
Photon detector (Photon detector (PMTsPMTs) ) detect optical photons detect optical photons and amplify the signals to produce electrical and amplify the signals to produce electrical current pulsecurrent pulse
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p45
ScintillatorScintillator
Airy Nothing. http://www.airynothing.com/high_energy_tutorial/detection/images/scintillator.gif (accessed October, 27, 2009).
Interactions of incoming Gamma-rays and scintillation crystal: Compton scattering Photoelectric effect Pair production The produced/recoiling
electrons have kinetic energy energy of visible photons
Scintillator TypesScintillator Types
OrganicOrganic LiquidLiquid
EconomicalEconomical MessyMessy
SolidSolid Fast decay timeFast decay time Long attenuation lengthLong attenuation length Emission spectraEmission spectra
Inorganic (Preferred)Inorganic (Preferred) NaI, CsINaI, CsI
Excellent Excellent resolution resolution Slow decay timeSlow decay time
BGOBGO High density, compactHigh density, compact
Special Nuclear Material http://carlwillis.files.wordpress.com/2008/07/fs_scintillator.jpg (accessed October, 27, 2009)
Photomultiplier tube (PMTs)Photomultiplier tube (PMTs)
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p108
PhotodiodePhotodiode
An alternative for An alternative for PMTs is PMTs is silicon silicon photodiodephotodiode
Electron-hole pairElectron-hole pair Electrons Electrons
anode (+)anode (+) Holes Holes cathode cathode
(-)(-) Movement of Movement of
electrons creates electrons creates detectable current detectable current
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p113
Coincidence Detection SystemCoincidence Detection System
Coincidence detection Coincidence detection system:system: Pair of gamma-rays Pair of gamma-rays
detector detector AmplifiersAmplifiers Pulse Height Pulse Height
Analyzer Analyzer Coincidence circuit Coincidence circuit
DetectorsDetectors detect detect gamma raysgamma rays
AmplifiersAmplifiers amplify amplify these electrical signalsthese electrical signals
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p16
Coincidence Detection SystemCoincidence Detection System
PHAPHA accepts photons accepts photons with selected above a with selected above a certain thresholdcertain threshold PHA generates a logic PHA generates a logic
pulse and feeds into a pulse and feeds into a coincidence circuitcoincidence circuit
Coincidence circuit Coincidence circuit analyzes pool of pulses to analyzes pool of pulses to find overlap = a find overlap = a coincidence coincidence Time period window Time period window
Coincidence event Coincidence event sent to 1sent to 1stst computercomputer for for data correction data correction
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p112
4 Types of Coincidences4 Types of Coincidences
True coincidence:True coincidence: Opposite direction Opposite direction
(~180(~180°°)) Scattered Scattered
coincidence:coincidence: One photon One photon
interacts with interacts with body and scattersbody and scatters
Misposition of the Misposition of the eventevent Maisey, M. Positron Emission Tomography and Basic Sciences. New
York: Springer, 2006, p126
4 Types of Coincidences4 Types of Coincidences
Random Random coincidence:coincidence: Separate Separate
annihilation annihilation eventsevents
Multiple Multiple coincidence:coincidence: Three or more Three or more
photons are photons are detected detected simultaneouslysimultaneously
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p126
Data CorrectionData Correction
Desired data Desired data truetrue coincidencescoincidences
ErrorsErrors randomrandom, , scatteredscattered, and , and multiplemultiple coincidences coincidences
One computer to One computer to correct data prior to correct data prior to sending to another sending to another computer for image computer for image reconstruction reconstruction
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p16
Image ReconstructionImage Reconstruction
BackprojectionBackprojection:: Each image pixel in (x, y) position at projection angle Each image pixel in (x, y) position at projection angle ФФ, r is , r is
calculated by the equation: calculated by the equation: r r = = x x sinФ + sinФ + y y cosФcosФ The backprojected image pixel A(x,y) is calculated by using the The backprojected image pixel A(x,y) is calculated by using the
equation equation
Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p13
PET ScannerPET Scanner
Canadian Agency for Drugs and Technology in Health. http://www.cadth.ca/media/healthupdate/issue1/hta_update_pet_scanner.jpg (accessed October, 27, 2009)
Applications of PET in MedicineApplications of PET in Medicine
Various areas of clinical Various areas of clinical diagnosis and diagnosis and management:management: Cancer diagnoses and Cancer diagnoses and
management management Cardiology and cardiac Cardiology and cardiac
surgerysurgery Neurology and Neurology and
psychiatrypsychiatry Drug development and Drug development and
regulation:regulation: Drug distributionDrug distribution Process of clearing Process of clearing
drugs by our body drugs by our body
A B
Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p10
Application of PET in Staging Lung Application of PET in Staging Lung AdenocarcinomasAdenocarcinomas
TNM staging system:TNM staging system: T – tumor sizeT – tumor size N – lymph node involvementN – lymph node involvement M – metastasisM – metastasis
Cancer staging can also be divided into:Cancer staging can also be divided into: Clinical stage Clinical stage c-stage c-stage Pathologic stage Pathologic stage p-stage p-stage
Tumor genes that are often associated with proliferative Tumor genes that are often associated with proliferative activity of cancer:activity of cancer: Ki-67Ki-67 Cyclin D1Cyclin D1 p53p53
Application of PET in Staging Lung Application of PET in Staging Lung AdenocarcinomasAdenocarcinomas
71 patients (c-stage IA lung 71 patients (c-stage IA lung adenocarcinomas with a tumor size adenocarcinomas with a tumor size range of 1-3 cm)range of 1-3 cm)
Contrast ratio (CR) value = index of Contrast ratio (CR) value = index of FDG uptakeFDG uptake CR = (T-N)/(T+N)CR = (T-N)/(T+N) T – ROIT – ROI N – contralateral lung N – contralateral lung
Immunohistochemical analysis with Immunohistochemical analysis with staining scores from 0 to 3 for three staining scores from 0 to 3 for three genesgenes 0 – none0 – none 1 – weak intensity 1 – weak intensity 2 – intermediate intensity2 – intermediate intensity 3 – strong intensity3 – strong intensity
Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Uno K. Japanese Journal of Clinical Oncology 2004;45:98–105.
ResultsResults
CR value is proportional to the invasion of the tumor The staining score of Ki-67 shows a positive correlation with the
invasiveness Staining scores of p53 and Cyclin D1 do not show significance
difference between different stages
Watanabe, Ken-ichi. Japanese Journal of Clinical Oncology ,2004;45:19–27.
Correlation between CR and Ki-Correlation between CR and Ki-6767
Data from the table are used to construct a calibration curve between CR values and Ki-67 staining score
The curve with a slope of 0.42 indicates a strong correlation between CR values and Ki-67 staining score
Thus, it is possible to use PET as a tool to diagnose stage of lung adenocarcinomas as well as how proliferative these adenomas are.
Watanabe, Ken-ichi. Japanese Journal of Clinical Oncology ,2004;45:19–27.