Positron Emission Tomography (revised)

Positron Emission Tomography (PET) Bringing the Invisible to Light Created By: Hung Vo Date: 11/02/2009 Course: Chem 717 - Instrumental Analysis

What is Emission Tomography?

PET

SPECT

MRI

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).

Key steps in ET study 

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Radiopharmaceutical production:  Create radiotracers Administration of radiopharmaceutical:  Injection, inhalation  Higher amount = better quality  Safety dose Data acquisition:  Imaging hardware record and detect gamma-rays  Stored as projection measurements Image reconstruction:  Filtered back projection (FBP)  creates tomographic images from projection data Image analysis:  Image are analyzed for desired data or statistics

Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004. p14

Radiotracers 

Unstable radioisotopes undergo radioactive decay  

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Nucleus is unstable Change in the number of protons or neutrons to form a more stable configuration

For example: 18F-FDG (Flourine-18fluorodeoxyglucose)  

FDG is an analog of glucose 18 F is unstable radioisotopes that emits positron Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p24

Radioactive decay 

Alpha decay:

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Beta decay:

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Positron decay:

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Electron capture:

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Isometric transition Saha, B. Basics of PET Imaging Physics, Chemistry, and Regulations. New York: Springer, 2005, p4

Annihilation Process  

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Positron comes to rest Combine with an e-  two photons (0.511 MeV) traveling in opposite direction (~180°) Gamma-ray region

Saha, B. Basics of PET Imaging Physics, Chemistry, and Regulations. New York: Springer, 2005, p6

General Mechanism of PET Scanner

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 Ring Detector in PET scanner? 

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To measure (xr, Ф) (sonogram) PET measures sonogram by electronic collimation Coincidence event Site of decay event is along the line

Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p36

Scintillation Detectors

Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p45

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Scintillator  convert high-energy photons into low-energy photons (in visible region) Photon detector (PMTs)  detect optical photons and amplify the signals to produce electrical current pulse

Scintillator 

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

Airy Nothing. http://www.airynothing.com/high_energy_tutorial/detection/images/scinti (accessed October, 27, 2009).

Scintillator Types 

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Organic  Liquid  Economical  Messy  Solid  Fast decay time  Long attenuation length  Emission spectra Inorganic (Preferred)  NaI, CsI  Excellent γ resolution  Slow decay time  BGO  High density, compact

Special Nuclear Material http://carlwillis.files.wordpress.com (accessed October, 27, 2009)

Photomultiplier tube (PMTs)

Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p108

Photodiode 

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An alternative for PMTs is silicon photodiode Electron-hole pair  Electrons  anode (+)  Holes  cathode (-) Movement of electrons creates detectable current

Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p113

Coincidence Detection System 

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Coincidence detection system:  Pair of gamma-rays detector  Amplifiers  Pulse Height Analyzer  Coincidence circuit Detectors  detect gamma rays Amplifiers  amplify these electrical signals

Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p16

Coincidence Detection System 

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PHA  accepts photons with selected above a certain threshold  PHA generates a logic pulse and feeds into a coincidence circuit Coincidence circuit analyzes pool of pulses to find overlap = a coincidence  Time period window Coincidence event  sent to 1st computer for data correction Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p112

4 Types of Coincidences 

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True coincidence:  Opposite direction (~180°) Scattered coincidence:  One photon interacts with body and scatters  Misposition of the event

Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p126

4 Types of Coincidences 

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Random coincidence:  Separate annihilation events Multiple coincidence:  Three or more photons are detected simultaneously

Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p126

Data Correction 

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Desired data  true coincidences Errors random, scattered, and multiple coincidences One computer to correct data prior to sending to another computer for image reconstruction Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p16

Image Reconstruction 

Backprojection: Backprojection:  Each image pixel in (x, y) position at projection angle Ф, r is calculated by the equation: r = x sinФ + y cosФ  The backprojected image pixel A(x,y) is calculated by using the equation

Wernick, N., and John N. A. Emission Tomography The Fundamentals of PET and SPECT. New York: Academic Press, 2004, p13

PET 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 Medicine A 

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Various areas of clinical diagnosis and management:  Cancer diagnoses and management  Cardiology and cardiac surgery  Neurology and psychiatry Drug development and regulation:  Drug distribution  Process of clearing drugs by our body

B

Maisey, M. Positron Emission Tomography and Basic Sciences. New York: Springer, 2006, p10

Application of PET in Staging Lung Adenocarcinomas 

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TNM staging system:  T – tumor size  N – lymph node involvement  M – metastasis Cancer staging can also be divided into:  Clinical stage  c-stage  Pathologic stage  p-stage Tumor genes that are often associated with proliferative activity of cancer:  Ki-67  Cyclin D1  p53

Application of PET in Staging Lung Adenocarcinomas 

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71 patients (c-stage IA lung adenocarcinomas with a tumor size range of 1-3 cm) Contrast ratio (CR) value = index of FDG uptake  CR = (T-N)/(T+N)  T – ROI  N – contralateral lung Immunohistochemical analysis with staining scores from 0 to 3 for three genes  0 – none  1 – weak intensity  2 – intermediate intensity  3 – strong intensity

Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Uno K. Japanese Journal of Clinical Oncology 2004;45:98–105.

Results Watanabe, Ken-ichi. Japanese Journal of Clinical Oncology ,2004;45:19–27.

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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

Correlation between CR and Ki67

Watanabe, Ken-ichi. Japanese Journal of Clinical Oncology , 2004;45:19–27.

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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.