Tomography is imaging by sections. 1

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3 Tomography is imaging by sections. 1 It is a technique used in clinical medicine and biomedical research to create images that show how certain tissues are performing their physiological functions. 1 Conversely, x-ray techniques construct images of anatomy thus only provide morphological information. 1 PET has greatly influenced surgical decision making in many as 40% of patients Manji Nekmohamed. Simultaneous Correction for Scatter and Attenuation in Positron Emission Tomography Using Statistical Image Reconstruction Methods. McMaster University Yuman Fong, et al. Utility of 18F-FDG Positron Emission Tomography Scanning on Selection of Patients for Resection of Hepatic Colorectal Metastases. The American Journal of Surgery 1999;178:282-7.

4 Concept of PET It is a medical imaging method for measuring spatial and temporal distribution of positron emitting isotopes. Body-penetrating photons produced from positron decay provide a way to image biochemical transformations in the living human body. 1 What is a Positron? A positron is an anti-matter electron, identical to the electron in mass, but has an opposite charge of Manji Nekmohamed. Simultaneous Correction for Scatter and Attenuation in Positron Emission Tomography Using Statistical Image Reconstruction Methods. McMaster University 2001

5 Cyclotron Unstable nuclei as it has too many protons so one of the protons decays as follows: Proton p + n o ñ e + Neutron Neutrino 1. Manji Nekmohamed. Simultaneous Correction for Scatter and Attenuation in Positron Emission Tomography Using Statistical Image Reconstruction Methods. McMaster University 2001

511 kev When an unstable nuclei decays to a more stable

6 511 kev When an unstable nuclei decays to a more stable isotope, it releases energy in the form of kinetic energy. Unstable nuclei e - Stable nuclei e + ñ 511 kev 1. Manji Nekmohamed. Simultaneous Correction for Scatter and Attenuation in Positron Emission Tomography Using Statistical Image Reconstruction Methods. McMaster University 2001

7 In PET a molecule of particular biological interest is tagged with a positron-emitting isotope and is injected into the body. Four most commonly used radioisotopes are 18 F, 11 C, 13 N, and 15 O since they can be easily substituted directly onto biomolecules. 3 Substitution of these radioisotopes does not significantly alter the reaction time or the mechanisms of a molecule. So, the biological behavior of the molecule does not change much. 3 Fluorine-18 Radiotracer Production: H 2 18 O + Proton 18 F[F - ] 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.17

8 18 F-Fluoride is further used to synthesize 1-( 18 F)fluoro-2-deoxy-Dglucose ( 18 F-FDG) which is used to measure glucose metabolism. 3 (3) 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.21

Following is a simplified diagram comparing the behavior of glucose and

3 Glucose travels across the blood brain barrier by facilitated

With the help of hexokinase (HK) it produces adenosine triphosphate and

Although, 18 F- FDG undergoes facilitated transport and form 18 F-FDG 6-

9 Following is a simplified diagram comparing the behavior of glucose and 18 F-FDG in the brain. 3 Glucose travels across the blood brain barrier by facilitated transport and enters a cell. With the help of hexokinase (HK) it produces adenosine triphosphate and other metabolites that can leave the cell. Although, 18 F- FDG undergoes facilitated transport and form 18 F-FDG 6- phosphate, it gets trapped in the cell as it lack the hydroxyl group on carbon2. 3 (3) 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.23

Some examples of radioisotopes and tracer compounds are shown below: Isotope Tracer

activation studies 11 C Methionine Protein synthesis Oncology study of cancer 18 F

metabolism Bone Imaging Oncology, neurology, cardiology 13 N Ammonia Blood perfusion

capillary bed in the biological tissue. * Not all approved by Health Canada (4) 4.

10 Some examples of radioisotopes and tracer compounds are shown below: Isotope Tracer Compound Physiological Process Typical Application 15 O Water Blood perfusion Brain activation studies 11 C Methionine Protein synthesis Oncology study of cancer 18 F Sodium Fluoride Altered bone-forming tissue activities 18 F Fluoro-deoxyglucose Glucose metabolism Bone Imaging Oncology, neurology, cardiology 13 N Ammonia Blood perfusion Myocardial perfusion * Perfusion is the process of delivery of arterial blood to the capillary bed in the biological tissue. * Not all approved by Health Canada (4) 4. Introduction to PET Physics. University of Washington 1999

11 Detector Ring Gamma particles being recorded Typical PET Scanner Patient Bed

12 Scintillators: Materials that give off photons under γ radiation Properties of Scintillators:- Scintiallation decay time how fast does it give off photons? Photomultiplier Tubes detect the light(photons) from the Scintillators Light output How many photons per γ incidence?

13 Property Sodium Iodide Bismuth Germanate Lutetium oxyorthosili cate Photon yield per kev Scintillation decay time (ns)

14 Pick up photon emissions from the scintillators Generate an electrical signal Amplify the signal and send to the computer for processing

15 Data Acquisition Step 1-Detect Coincidence Events γ particles are released at 180 o to each other Pair of detectors on the opposite sides of the ring are activated within the sampling time window The point of annihilation must lie on the Line of Response (LOR) True Coincidences

16 Data Acquisition Step-2 Determine and store all LORs Y r Ф X Point of annihilation can be anywhere on LOR not possible to plot using X and Y. Each detector pair has fixed (X,Y) coordinates. Store each LOR in terms of (r, Ф) coordinates.

17 Sinograms Plot of all LORs is called a Sinogram Count for each pixel a unique LOR is incremented upon recurrence

18 Data Correction Incorrect coincidences are eliminated What is Random Coincidence? Two γ photons from different events are detected simultaneously Setup a wrong LOR Random Coincidence

19 Data Correction Incorrect coincidences are eliminated How to eliminate them? Probabilistic methods exist to estimate random coincidences Calculate and subtract from total LORs detected by every pair of detectors. Random Coincidence

20 Image Reconstruction Backprojection techniques Method 1: (r, Ф) (x,y) image pixel conversion r = x sin Ф + y cos Ф For each (x,y) at Ф, r is calculated For corresponding r, the recurrence count is transferred to (x,y) plane. Higher count events are re-inforced

21 Image Reconstruction Backprojection techniques Method 2: Backproject all LORs Areas with multiple LORs are reinforced

22 Filtering the image Blurring reduces the contrast and sharpness of the image Blurring shows up as a low frequency signal in frequency domain Image signal Fourier Transfrom Convolve with ramp filter Multiply by ramp function Inverse Fourier Transfrom New image with less blurring

23 Filtering the Image Ramp filter removes low frequency blurring But, also amplifies high frequency noise Hybrid filters

24 Image Reconstruction Filtered Backprojection example:-

25 Normal whole body distribution of 18 F-FDG. Intense tracer activity in the brain, heart, and bladder. Some neck and gastric activity can also be seen Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.112

26 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.112 (3)

27 A 66-year-old man with autoimmune pancreatitis. FDG PET in A shows intense FDG uptake in the pancreas (arrows). Image B is taken after steroid therapy, no uptake is observed in the pancreas. (3) 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.386,413

observed in the pancreas. (3) 3. Wahl L. Richard.

28 A 66-year-old man with autoimmune pancreatitis. FDG PET in A shows intense FDG uptake in the pancreas (arrows). Image B is taken after steroid therapy, no uptake is observed in the pancreas. (3) 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.386,413

dilated cardiomyopathy (disease of the heart muscle that causes the heart to be enlarged and pump less strongly).

29 Colour Scale: lowest to highest radioactivity concentration = black/blue/green/yellow/red. Yellow and red are normal. Transaxial images showing maximum uptake of 11 C- acetate in a healthy individual (A) and a patient with congestive heart failure due to dilated cardiomyopathy (disease of the heart muscle that causes the heart to be enlarged and pump less strongly). 11 C-acetate is enhanced in right ventricle (RV) in B. LV = Left ventricle. A (3) 3. Wahl L. Richard. Practice and Principles of Positron Emission Tomography. Lippincott Williams & Wilkins 2002; P.386,413

30 PET has poor image resolution compared to CT PET loses a lot of information due to scatter and random coincidence correction In a slice of tissue only a few major sections take up the radionuclide, restricting the detection of other surrounding sections.

31 PET/CT Application In CT scans we only know about the anatomy of the tissue No physiological information is provided. Combining PET and CT Doctor s treasure

32 Increased activity PET Image of a patient s thigh

33 No evidence of pathology CT Image of patient s thigh

34 Combined PET/CT image Infection located beside femur

35 PET/CT Application Advantages Better understanding of patient s condition CT data can be used to correct PET data loss due to scattering and attenuation Cheaper to implement a dual-camera modality

36 PET/CT Application Disadvantage PET camera in a dual-modality has lower resolution

37 Technological Innovations PET in 3-D already exists Combination of different imaging techniques to give high quality information:- PET/CT, PET/MRI, PET-CT-MRI Possible to create a complete biological model of the patient

39 Questions? Sure

Radionuclide Imaging MII Positron Emission Tomography (PET)

Radionuclide Imaging MII Positron Emission Tomography (PET) Radionuclide Imaging MII 3073 Positron Emission Tomography (PET) Positron (β + ) emission Positron is an electron with positive charge. Positron-emitting radionuclides are most commonly produced in cyclotron