Positron Emission Tomography (Revised)

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


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


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)


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


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


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


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


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


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


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


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.

Documents

Positron Emission Tomography (Revised)