BMED-4800/ECSE-4800 Introduction to Subsurface Imaging Systems

1. BMED-4800/ECSE-4800Introduction to Subsurface Imaging Systems Lecture 6: Nuclear Medicine Kai E. Thomenius1 & Badri Roysam2 1Chief Technologist, Imaging Technologies, General Electric Global Research Center 2Professor, Rensselaer Polytechnic Institute Center for Sub-Surface Imaging & Sensing

2. Homework #3:Using the “Faridana” (Adel Faridani) filtered back projection code example, change filter parameters for a lower bandpass. Demonstrate loss of spatial resolution. • http://people.oregonstate.edu/~faridana/preprints/preprints.html • A. Faridani: Introduction to the Mathematics of Computed Tomography. Inside Out: Inverse Problems and Applications, G. Uhlmann (editor), MSRI Publications Vol. 47, Cambridge University Press, 2003, pp. 1-46. • http://www.onid.orst.edu/~faridana/preprints/fbp.txt - MATLAB code for filtered back projection • Designer Shepp-Logan phantom • Filter design possibilities • Make sure to use the modified code (fbp2ket.m) available from http://www.ecse.rpi.edu/censsis/SSI-Course

3. Recap: CT & Filtered Backprojection Backprojection reconstruction w. no filtering. Impact of filter on Sinogram. Backprojection reconstruction w. filter, compare images.

4. Taking Stock of x-ray CT • X-ray images of a live or dead subject look the same! • the core contrast mechanism does not depend on activity, only on structure • Some activities can be sensed (e.g., gross movements can be sensed with cine x-ray) • The kinds of activities with the greatest medical value are of a biochemical nature • They involve the presence/absence, chemical state, spatial distribution, and movements of specific biochemicals in the body • This observation has driven the development of functional & molecular imaging methods.

5. Nuclear Medicine • Basic Idea: • Inject patient with radio-isotope labeled substance (tracer) • Chemically the same as a biochemical in the body, but physically different • Detect the radioactive emissions (gamma rays) • Super-short wavelength • But, can’t achieve the implied high resolution • Detection technology limitations • Not enough photons! • This can be done in 2D: scintigraphy • This can be done in 3D: SPECT/PET • Use filtered back-projection to reconstruct the 3-D image, just like x-ray CT

6. Nuclear Medicine • Imaging is done by tracing the distribution of radiopharmaceuticals within the body. • Radionuclides or radioisotopes are atoms that undergo radioactive decay, and emit radiation. • In nuclear medicine, we are interested in radionuclides that emit x-rays or gamma rays. • A radiopharmaceutical is a radionuclide bound to a biological agent.

7. Example: FDG • Fluorodeoxyglucose is a radiopharmaceutical is a glucose analog with the radioactive isotope Fluorine-18 in place of OH • 18F has a half life of 110 minutes • FDG is taken up by high glucose using cells such as brain, kidney, and cancer cells. • Once absorbed, it undergoes a biochemical reaction whose products cannot be further metabolized, and are retained in cells. • After decay, the 18F atom becomes a harmless non-radioactive heavy oxygen 18O– that joins up with a hydrogen atom, and forms glucose phosphate that is eliminated via carbon dioxide and water 2-Deoxy-D-Glucose (2DG)

8. What Happens Upon Radioactive Decay Basic Idea: • Nucleus emits a positron (an anti-electron) • A short-lived particle • Same mass as electron, but opposite charge • Positron collides with a nearby electron and annihilates • Two 511 keV gamma rays are produced • They fly in opposite directions (to conserve momentum) Gamma Photon #1 Nucleus (protons+neutrons) BANG electrons Gamma Photon #2

9. Gamma Ray – Matter Interactions • 3 basic mechanisms for photon - matter interaction: • Photoelectric Effect (transfer energy to an electron, ejecting it). For < 50KeV • Compton Scatter (lose energy to an electron, and creat e alower-energy photon). For 100KeV – 10MeV • Electron-positron pair Production (For > 1MeV) • Any one of these can happen to the radionuclide gamma-rays. Compton Scatter Pair Production

10. Energy of a Gamma Ray • A radionuclide has a typical energy: e.g. 140 keV for 99mTc • Detection of lower energy scattered gamma- or x-rays degrades contrast and image quality. • A radioisotope emits one (or more) very sharp energy lines

11. Effects of Gamma Rays on Tissue • Gamma rays cause ionization • Capable of causing damage at the cellular level • Actually used to ultra-sterilize equipment • Used to kill tumors (radiation therapy) • The greatest damage occurs in the 3 – 10MeV range • High energy gamma rays just pass throuigh the body and cause no damage

12. How do we Detect Gamma Rays? • Some crystals (sodium iodide) exhibit the property of scintillation. • Scintillation is a flash of light produced in a transparent material by an ionization event. • When a gamma ray strikes this crystal, it knocks an electron loose from an Iodine atom. • This electron then goes to a lower energy state, and in doing so, emits a faint burst if light • This faint burst of light can be detected using a sensitive device known as a photomultiplier tube (PMT). • Electronic circuits count the number of flashes and these numbers are used to reconstruct images.

13. Cross-section of an Anger Camera • Shield Around Head • Mounting Ring • Collimator Core • Sodium Iodide Crystal • Photomultiplier Tubes Named after Hal Anger

14. Cross-section of an Anger Camera

15. Collimator Design & Function Resolution v. Efficiency Trade-off

16. SPECT Instrument • The “gamma camera” is a 2-D array of detectors • One or more gamma cameras are used to capture 2-D projections at multiple angles • Use filtered back-projection to reconstruct 3-D image! • Actual sinograms appear “noisy” due to the fact that we don’t have enough photons • Quantum-limited imaging 3-camera SPECT instrument

17. Modern SPECT Scanners • GE Hawkeye DigiRad Mobile SPECT System

18. Nuclear Medicine Images • Typical image: • 64 by 64 pixels • Intensity gives “counts per pixel” • Pseudocolor often used. • Nuclear med imaging modes: • Static • Dynamic • MUGA • Whole Body • SPECT

19. Whole Body Imaging • Bright spots indicate regions where the radioisotope is bound

20. Cardiac Study

21. Cardiac Study • Evaluation of the coronary artery circulation • Myocardial perfusion • 3D Studies of the radionuclide activity

22. Nuclear Medicine Performance Metrics • Typical performance: • Energy resolution: 9.5 – 10% • FWHM response • Spatial resolution: 3.2 – 3.8 mm • Uniformity: 2 – 4%

23. Strengths & Limitations of SPECT • Main Strengths: • Low cost: cheaper instrumentation & cheaper longer-lived and easily obtained radio-pharmaceuticals • quick acquisition and simple reconstruction • Can be made nearly portable • Can be shaped to suit custom applications • Can be made to acquire time series • Can be gated to sync with other signals (e.g., ECG) • Multiple camera heads (typ. 2 – 3) can speed up acquisition • Main Weakness: • Low resolution: Reconstructed images typically have resolutions of 64×64 or 128×128 pixels, with the pixel sizes ranging from 3–6 mm.) • Attenuation of gamma rays leads to underestimation of activity in deep regions • Intense areas of activity result in a lot of “streaking” artifacts

24. Ways to Improve Upon SPECT • Better reconstruction algorithms • Model the point spread of photons more accurately • Model the non-uniform attenuation of gamma rays in the body (leveraging x-ray CT) • Build combo “x-ray CT & SPECT” systems • Use both the photons: PET • Since a pair of gamma rays at 180o are produced, try to detect pairs of photons instead of single photons • Detect photon timing: TOF-PET • The difference in photon arrivals can tell us where the decay event occurred!

25. Better Algorithms • Filtered back-projection algorithm • produces a background artifact, discussed earlier • Noisy reconstruction • The Maximum Likelihood algorithm produces a better reconstruction for the same data Filtered Back-Projection Maximum Likelihood

26. Positron Emission Tomography: PET • Several gamma-detector rings surround the patient. • When one of these detects a photon, a detector opposite to it, looks for a match. • Time window for the search is few nanosecs. • If such a coincidence is detected, a line is drawn between the detectors. • When done, there will be areas of overlapping lines indicating regions of radioactivity.

27. B A Emission Detection Ring of detectors • If detectors A & B receive gamma rays at the approx. same time, we have a detection • Hard sensor and electronics design problem, expensive

28. Image Reconstruction • We can sort our set of detections by angle, and view the data as a set of angular projections • Use filtered back-projection algorithm!

29. PET Images • Single-channel images • Noisy, and blurry • Not ideal for segmentation • Segment MRI/CT for defining anatomy • Register the images • Measure activity

30. PET Radiotracers • 18FDG is probably the most widely used PET tracer. • HIGH FDG pick-up by tumors first reported in 1980 at Brookhaven NL. • Can also be used to measure rate of metabolism in the brain.

31. Application in Lung Cancer • Case Study: • 55-year old female • Lung Cancer • 2 cycles of chemo & radiotherapy • PET results: • Increased uptake of FDG in lung nodules • Increased uptake of FDG in lymph nodes • Therapy will have to be continued.

32. SPECT vs PET • Both are Major Functional imaging tools • SPECT: Single-photon Emission Computed Tomography • cheap and low-resolution • Tells us where blood is flowing • PET: Positron Emission Tomography • expensive but higher-resolution PET image Showing a tumor

33. How Does PET Compare With Other Imaging Modalities? • PET provides images of molecular-level physiological function • Extends capabilities of other modalities. • Like MR & CT, it uses tomographic algorithms • Like Nuclear Medicine, the images represent distributions of radiotracers. • But that’s where the similarity ends… CT Scan MRI Scan PET Scan Report: Patient Deceased. Report: Normal Report: Normal

34. Other Imaging Instruments • Structure imaging: • CT & Magnetic Resonance Imaging • Ultrasound Imaging • Functional Imaging: • Nuclear Imaging • Positron Emission Tomography • Single-Photon Emission Computed Tomography • Combined Modalities • Functional & structural imaging • 1999 image of the year, U. of Pittsburgh

35. PET/CT Scanners • Generation of PET & CT images in a single study • The image data sets are registered and fused. • Anatomic data from CT • Metabolic data from PET • Colorectal Cancer shown in images.

36. Steps in imaging • Imaging done by a gamma camera. • A radionuclide is infused into the patient’s blood. • Usually, the radionuclides have a specific physiological role. • This gives the clinical specificity to the procedure. • Concentrations of the agent emit greater quantity of gamma rays. • These are mapped by the camera head.

37. Source Material • http://apps.gemedicalsystems.com/geCommunity/nmpet/nmpet_neighborhood.jsp • Siemens & Philips web sites for nuclear medicine & PET • http://www.crump.ucla.edu/software/lpp/lpphome.html • http://thayer.dartmouth.edu/~bpogue/ENGG167/13%20Nuclear%20Medicine.pdf

38. Summary • Introduction to Nuclear Medicine, SPECT and PET imaging. • Additional examples of agents (probes) introduced to reveal subsurface phenomena. • Today’s focus on radioactive labeling. • Review of instruments • Relatively straightforward devices. • Signal-to-noise ratio challenges, need to limit exposure. • Powerful clinical tools. • Much of today’s research focused on PET and extensions of PET technology.

39. Instructor Contact Information Badri Roysam Professor of Electrical, Computer, & Systems Engineering Office: JEC 7010 Rensselaer Polytechnic Institute 110, 8th Street, Troy, New York 12180 Phone: (518) 276-8067 Fax: (518) 276-6261/2433 Email: roysam@ecse.rpi.edu Website: http://www.ecse.rpi.edu/~roysabm Secretary: Laraine Michaelides, JEC 7012, (518) 276 –8525, michal@rpi.edu

40. Instructor Contact Information Kai E Thomenius Chief Technologist, Ultrasound & Biomedical Office: KW-C300A GE Global Research Imaging Technologies Niskayuna, New York 12309 Phone: (518) 387-7233 Fax: (518) 387-6170 Email: thomeniu@crd.ge.com, thomenius@ecse.rpi.edu Secretary: Laraine Michaelides, JEC 7012, (518) 276 –8525, michal@rpi.edu