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  • 1.Physics of nuclear medicine introduction historic and current NM technologies principle of gamma camera image quality and gamma camera performance characteristics gamma camera QC data acquisition and processing methods SPECT and SPECT/CT other devices Physics of nuclear medicine Cherry SR, Sorenson JA, Phelps ME, Physics in Nuclear Medicine 3rd ed (2003) Chapters 12, 13, 14, 15, and 17 Introduction of nuclear medicine radiopharmaceutical (a radionuclide attached to a chemical compound) administered to patient, then (hopefully) concentrated to the abnormal sites through interaction between the pharmaceutical and cells or molecules decay of the radionuclide in the sites: emitting of single or annihilation photons detection of the emitted photons using gamma camera, PET scanner or other devices Introduction of nuclear medicine sensitive to functional changes earlier detection of diseases and exclusive diagnostic capability, e.g. perfusion for heart, brain, kidney and lungs, and metabolism for cancers interaction at cellular or molecular levels bound directly to a target molecule (111In- monoclonal antibody), low sensitivity accumulated by molecular or cellular activities of the target (18F-FDG, 99mTc-sestamibi, 131I), high sensitivity

2. Introduction of nuclear medicine emitted photon energy: 70 to 511 keV most low-energy photons absorbed by tissues most high-energy photons penetrating the detector charged particles penetrating only mm of tissue pixel value of the image: concentration of radioactivity may need post-acquisition data processing poorer image quality due to limited photon number and poor spatial resolution History of nuclear medicine 1895 discovery of x-ray by Roentgen 1896 discovery of radioactivity by Bequerel 1898 production of radium by Curie 1927 use of radon to measure the blood transit time 1930s invention of cyclotron by Lawrence 1945 invention of nuclear reactor 1951 rectilinear scanner to acquire images History of nuclear medicine 1958 invention of Anger camera 1964 use of Tc-99m (I-131 only prior to 1964) Tc-99m: metastable (T1/2 = 6.01 hr) pure decay (E = 140 keV), flexible for labeling I-131: electrons and 364 keV photons, thyroid disorders only 1970 derivation of image reconstruction algorithm for tomography (CT, SPECT, PET) 1998 rapid spread of PET and PET/CT The most often used radionuclide: Tc-99m metastable state of 99Tc43: T1/2 = 6.01 hr long enough for imaging but short for reduced radiation dose to patient pure decay: less radiation dose E = 140 keV: enough photons to escape from the patient body but most stopped by the detector flexible for labeling (attached to a pharmaceutical): wide clinical applications 3. The most often used radionuclide: Tc-99m The first rectilinear scanner (1951) The first Anger camera (1958) Dual-head gamma camera 4. SPECT gamma camera Two detectors mounted on a rotation gantry with different angles (180, 90) for tomography Mobile semiconductor gamma camera 152010 cm CZT detector breast imaging sports medicine ER and OR imaging 3000 0.30.3 cm discrete crystals 48 PSPMT Planar imaging Tc-99m sestamibi 3 mm lesion detectable Tc-99m MDP Dynamical imaging a series of images with time 5. SPECT imaging transaxial coronal sagittal SPECT imaging short-axis vertical long-axis horizontal long-axis Pros and cons of nuclear medicine inherent molecular imaging high sensitivity low concentration of radionuclide ~ pmol/liter biodistribution depends not only on the specificity of the carrier but also on the route of administration. noisy and suboptimal resolution Molecular imaging ACR definition: Spatially localized and/or temporally resolved sensing of molecular and cellular processes in vivo. SNM definition: Visualization, characterization, and measurement of biological processes at the molecular and cellular levels in human and other living systems. 2-D or 3-D imaging and variation over time Including NM, PET, MRI, MRS, optical, US and CT with contrast 6. Molecular imaging modalities resolution ____ modality sensitivity spatial temporal contrast MRI + 10-100m msec +++ MRS + 1 cm min-h + PET +++ 3-4 mm min ++ SPECT ++ 8-12 mm min + optical +++ 1-2 mm msec +++ US +++ 1 mm msec ++ +++: high, ++: medium, +: low Probes for molecular imaging bound directly to a target molecule accumulated by molecular or cellular activities of the target activated by the target enzyme in vivo Smart NIR agents With specific enzyme cleavage, fluorophores are separated from the backbone and each other so as to markedly increase their fluorescence. Gamma camera pat ient collimat or det ect or PMT pre- amp amp & sum posit ionPHA comput er display X Y Z 7. Major components collimator to establish position relationship between photon source and detector (projection imaging) scintillation detector (NaI(Tl)) to convert x or photons to blue light photons photomultiplier tube (PMT) to convert blue photons to electrons and to increase the number of electrons electronics to amplify and discriminate electrical signals display to display the image acquired by gamma camera Collimator to establish position relationship between the source and detector poor spatial resolution (ability to see details) and low detection efficiency (ability to count photons) The weak link of a gamma camera: The collimator determines the resolution and sensitivity of a gamma camera. Collimator design principle: to optimize the trade-off between resolution R and sensitivity hole size d and hole length l smaller (or longer) holes higher R but lower septal thickness t penetration < 5% hole orientation: parallel-hole, converging, diverging pinhole: single hole d t Parallel-hole collimator increasing source-to-detector distance leads to same sensitivity same FOV same image size lower R 8. Converging beam collimator increasing source-to-detector distance leads to decreasing FOV increasing image size lower R higher sensitivity FOV F fan cone Pinhole collimator increasing source-to-detector distance leads to increasing FOV decreasing image size lower R lower sensitivity FOV NaI (Tl) detector energy spectrum scintillation process to convert photons to blue photons (E 3 ev or 415 nm) theoretical deposited energy spectrum in detector photopeak: completely absorbed compton edge: Ee = E0 Es (at 180) above the edge: multiple scatter below the edge: single + multiple NaI (Tl) detector energy spectrum photopeak single scatter double scatter p.e p.e c.s c.s Compton edge c.s c.s c.s c.s 9. NaI (Tl) detector energy spectrum actual deposited energy spectrum in detector spread photopeak caused by imperfect energy resolution (random fluctuation of blue photon number in detector) backscatter peak due to photon penetrating the detector, backscattered by surrounding material, reentering detector, and absorbed by the detector: Eb + Ee = E0 iodine escape peak 30 keV K-shell x-rays following p.e. absorption of iodine: Ee E0 30 keV lead K-shell x-ray (80 90 keV) following p.e. in lead NaI (Tl) detector energy spectrum backscatter iodine escape lead x-rays p.e c.s p.e p.e NaI x-ray x-rayp.e e x NaI (Tl) detector energy spectrum Hg-197 w.o. scatter I-131 w/w.o. scatter Advantages of NaI (Tl) detector good stopping power for low-energy ( = 3.67 g/cm3, Zeff = 50, PE dominant) = 16.58 cm-1 @ 69 keV, t = 0.95 cm, T 0% = 2.57 cm-1 @ 140 keV, t = 0.95 cm, T = 7.7% = 0.72 cm-1 @ 247 keV, t = 0.95 cm, T = 48.5% good detector linearity over 20 - 2000 keV good conversion efficiency: ~ 26 eV/blue photon good transparent to blue photons blue photons matched with the performance of PM tube easy to manufacture 10. Disadvantages of NaI (Tl) detector poor stopping power at E > 200 keV slow scintillation decay (230 ns) low counting rate Compton scatter dominated at E > 250 keV poor spatial resolution fragile must keep dry Photomultiplier tube to create and amplify e-pulse photocathode (CsSb): blue light to electrons 9 - 12 dynodes: each increasing electrons 3 6 times anode: collect electrons: 610 6 107 NaI(Tl) 0 + 3 0 0 v + 4 0 0 v + 5 0 0 v + 6 0 0 v + 7 0 0 v cathod anode dynode To preamplifier Photomultiplier tube stable high voltage 1200 V needed for 10 dynodes 1% increase of high voltage 10 % increase of current at anode sealed in glass and evacuated wrapped in Mu-metal (alloy of Fe, Ni, Cu) to shield magnetic field magnetic field affecting focusing of electron beam Photomultiplier tube 40 to 100 PM tubes (d = 5 cm) in a modern gamma camera photocathod directly coupled to detector or connected using plastic light guides anode connected to electronics in the tube base ultrasensitive to magnetic field 11. Electronics preamplifier to amplify pulses from the PM tube to match impedances between the detector and subsequent components to shape pulses for subsequent processing voltage- and charge-sensitive circuits amplifier to amplify pulses from mV to V to reshape slow decay pulses to narrow ones using resistor-capacitor circuit baseline restoration circuit Electronics pulse height analyzer: selecting the pulses of certain voltage amplitudes (channel) to discriminate against unwanted photon lower-level discriminator upper-level discriminator anticoincidence circuit 1 2 3 V2 (154 keV) V1 (126 keV) Electronics position circuit x y Z YY ky Z XX kx YYXXZ i i i i y i i i i x i i i i i i i i + + ++ = = +++= Display cathode ray tube (CRT) linearity dynamic range contrast brightness LCD: thin film transistor (TFT) plasma display e- source anode def lect ion plates screen z y x 12. Detection of a -photon 1 -photon 1 electrical pulse (1 count) The photon may experience p.e in the detector (A), c.s in the detector (B), or c.s in the patient (C). energy deposited on the detector # blue photons pulse height entire energy maximum pulse height (A) partial energy reduced pulse height (B, C) A B C BA C Image quality main factors of image quality: 1. contrast: the difference in count density between two objects (or ba