PET/MRI Principle, History, and Perspective. Main Imaging Techniques. X-ray Tube. History of X-ray & CT. How to Look inside the Human Body

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tube threaded through body) Possible damage or trauma (bloody!

1 PET/MRI Principle, History, and Perspective Jae Sung Lee, PhD Dept. of Nuclear Medicine and Biomedical Sciences WCU Dept. of Brain and Cognitive Sciences Seoul National University Basic Imaging Principles How to Look inside the Human Body Invasive techniques Direct cutting the body through surgery Endoscope (a light tube threaded through body) Possible damage or trauma (bloody!!!) Non-invasive (or less invasive) techniques Tomography Derived from the Greek word tomos which means "a section" or "a cutting" Basic Imaging Principles Main Imaging Techniques 1.2 Physical Signals <> Shorter wavelength & higher energy X-ray transmission or CT Magnetic resonance imaging (MRI) Nuclear medicine or gamma ray emission 700 nm 600 nm 500 nm 400 nm 1.1 History of Medical Imaging History of X-ray & CT X-ray Tube Discovery & early applications Discovery of x-rays by Wihelm C Roentgen (Dec, 1895) First clinical use of x-ray (Feb, 1896) Wide use of static & dynamic (fluoroscopic) techniques X-ray CT Image reconstruction algorithm by Allan Cormack (US) First true CT scanner by Godfrey Hounsfield (EMI in UK, 1972) Nobel Prize in Medicine (1979) 1

2 Radiographic Procedures X-ray detector X-ray tube Transmission imaging with x-ray Chest x-ray unit (a) and image (b) : overlay (or superimposed) body structures on 2D image 1.5 Computed Tomography (CT) 1.5 Computed Tomography (CT) Computed Tomography (CT) Tomography Derived from the Greek word tomos which means "a section" or "a cutting" Types of CT Single slice (standard) CT Helical CT: rapid acquisition for whole-body Multi-slice CT: cone-beam x-ray projection for rapid 3D imaging GB Liver Spine CT scanner (a) and (b) a CT image of a slice through the liver Stomach Spleen Rib FBP Reconstruction: Back-Projection 2 projection 4 projection 8 projection θ θ r 60 projection 180 projection Original 2

1.1 History of Medical Imaging History of Nuclear Medicine Early discoveries Discovery of radioactivity by A.

medical use in 1961) Courtesy of Siemens Medical First scanners Rectilinear scanner, the first imaging system, by Benedict Cassen at UCLA Anger

undergoes radioactive decay, and emits a gamma ray(s) and/or subatomic particles to be stabilized.

Glucose [ 18 F]flurodeoxyglucose l (FDG) CH 2 O CH 2 O 18 F Unstable & radioactive 19 F: stable Nuclear Medicine Imaging Nuclear medicine

3 1.1 History of Medical Imaging History of Nuclear Medicine Early discoveries Discovery of radioactivity by A. Henry Becquerel in 1986 Radioactive tracer technique by George de Hevesy in 1923 Discovery of Tc-99m by Perrier and Emilio Segre in 1937 (first medical use in 1961) Courtesy of Siemens Medical First scanners Rectilinear scanner, the first imaging system, by Benedict Cassen at UCLA Anger scintillation camera by Hal Anger at UC Berkeley in 1952 Radioisotope Atom with an unstable nucleus with excess energy The radionuclide undergoes radioactive decay, and emits a gamma ray(s) and/or subatomic particles to be stabilized. Radiopharmaceutical (=Radiotracer) Radioactive compound used for the diagnosis and therapeutic treatment of human diseases. Glucose [ 18 F]flurodeoxyglucose l (FDG) CH 2 O CH 2 O 18 F Unstable & radioactive 19 F: stable Nuclear Medicine Imaging Nuclear medicine procedures Injection of pharmaceutical with a radioactive substance attached The radio-pharmaceutical tracks a particular process in your body. The gamma camera produces a picture of body, showing where the tracer has accumulated. Nuclear medicine lung scan 3

Beta Plus (Positron, β ) Emission Positron Emission & Mutual Annihilation 511 kev γ-ray 11 C v

Electron (β-) Einstein s mass-energy equivalence 511 kev γ-ray PET Emission Detection Advantages of

yes Line of response (LOR) Accurate alignment of anatomic and functional images available

PET Limitations of PET/CT Radiation exposure during the PET/CT ~ twice as much as standalone PET or

Not a truly simultaneous scan, but sequential Same physical principles in PET and CT detectors

1 History of Medical Imaging History of MRI Nuclear magnetic resonance Felix Bloch & Edward Purcell:

imaging Suggestion for medical use by Raymond Damadian in 1973 Paul Lauterbur (1 st MRI) & Peter

4 Beta Plus (Positron, β ) Emission Positron Emission & Mutual Annihilation 511 kev γ-ray 11 C v Neutrino 6 protons 5 neutrons Neutron poor 5 protons 6 neutrons Positron 11 B Positron (β) E=mc 2 Electron (β-) Einstein s mass-energy equivalence 511 kev γ-ray PET Emission Detection Advantages of Combined PET/CT PET CT PET/CT Coincidence? yes Line of response (LOR) Accurate alignment of anatomic and functional images available immediately after the scans Reduction of PET scan time by using the CT for attenuation correction of PET Limitations of PET/CT Radiation exposure during the PET/CT ~ twice as much as standalone PET or CT PET/MRI will be potentially useful in Pediatric studies Repeated scans for treatment monitoring Not a truly simultaneous scan, but sequential Same physical principles in PET and CT detectors Crosstalk from x-ray CT on PET CT has lower soft tissue contrast than MRI. 1.1 History of Medical Imaging History of MRI Nuclear magnetic resonance Felix Bloch & Edward Purcell: 1952 NP in Physics (discovery of NMR in 1946) Richard Ernst: 1991 NP in Chemistry (MRI concept) MR imaging Suggestion for medical use by Raymond Damadian in 1973 Paul Lauterbur (1 st MRI) & Peter Mansfield (EPI, echo planar imaging, technique) : 2003 NP in Medicine MR angiography (MRA) by Charles Dumoulin (1987) Functional MRI (fmri) in 1993 Hyperpolarized Xe-129 gas for respiration studies in

1.8 Magnetic Resonance Imaging (MRI) Magnetic Resonance Imaging (MRI) Principles Selective excitation of hydrogen atom in the body Creation of little magnets Precession of protons while returning

oxidation imaging NMR Origin of MR Signals 1 H, 13 C, 19 F, 31 P Hydrogen, carbon, fluorine, phosphorus Prevalent in biological systems: enough signal 1 H (single proton) in MRI Very high density in

5 1.8 Magnetic Resonance Imaging (MRI) Magnetic Resonance Imaging (MRI) Principles Selective excitation of hydrogen atom in the body Creation of little magnets Precession of protons while returning back Generation of radio-frequency EM signals Operation modes Standard MRI Echo-planar imaging (EPI): real time imaging Magnetic resonance spectroscopic imaging (MRS) Functional MRI (fmri): blood oxidation imaging NMR Origin of MR Signals 1 H, 13 C, 19 F, 31 P Hydrogen, carbon, fluorine, phosphorus Prevalent in biological systems: enough signal 1 H (single proton) in MRI Very high density in body due to H 2 O content Very strong NMR signal due to high gyromagnetic ratio (γ ) Nuclear Magnetization No external magnetic field No preferred orientation for nuclei Randomly oriented nuclear spins No net macroscopic M-field in spin system Nuclear Magnetization (cont ) Applied external magnetic field (B 0 ) Alignment of microscopic spins 2 orientations: 54 or 126 (180-54) degree off z Slight preference for 54º ( up : low energy state) Random phase (orientation around z-axis) of μ Overall spin system: slightly magnetized in z direction ( bulk or macroscopic magnetization) RF Excitation How to produce magnetization vector M that are not parallel to B 0 B 0 z z z M B M 0 B 0 M Relaxation Definition Decay of MR signal after application of RF-pulse Mechanisms Transverse or spin-spin p relaxation (T 2 ) Longitudinal or spin-lattice relaxation (T 1 ) z B 0 x y x B 1 Turn on small magnetic field in x direction y x B 1 Motion of M(t) in y direction y x M y In the rotating coordinate 5

Higher Soft Tissue Contrast in MRI Superior diagnostic accuracy,

Useful in local tumor assessment and whole-body staging where the

crystal 0 V 100 V 300 V 500 V 700 V Radiation 200 V 400 V 500 V

visible light photons into an electrical signal at photocathode

(PMT) High gain (~10 6 ) and stable Bulky and very sensitive to

Field PMT: photomultiplier tube (conventional photosensor in PET)

small Low gain (10 2 ~10 3 ) and timing resolution (> 2-3 ns)

6 Higher Soft Tissue Contrast in MRI Superior diagnostic accuracy, particularly in brain studies Higher Soft Tissue Contrast in MRI Useful in local tumor assessment and whole-body staging where the higher soft tissue contrast of MRI is beneficial X-ray CT MRI X-ray CT MRI Barentsz et al., JCO, 2006 Positron Emission Tomography (PET) Scintillation crystal 0 V 100 V 300 V 500 V 700 V Radiation 200 V 400 V 500 V Visible Light Photon Photomultiplier tubes (PMT) Conversion of visible light photons into an electrical signal at photocathode Signal amplification Photo-sensors for PET Photo-Multiplier Tube (PMT) High gain (~10 6 ) and stable Bulky and very sensitive to magnetic field Conventional PMT in Magnetic Field Out of magnetic Field PMT: photomultiplier tube (conventional photosensor in PET) Avalanche Photodiode (APD) Insensitive to magnetic field and small Low gain (10 2 ~10 3 ) and timing resolution (> 2-3 ns) Geiger-mode APD (G-APD) Higher gain (10 5 ~10 6 ) Fast pulse rise time (<1 ns) In magnetic Field N S Lorentz Force!!! Kwon SI,

Gachon PET/MRI (Concept) Gachon PET/MRI (Implementation) Magnetic

(Proteomics, 2008) HRRT-PET-Side Railway Middle Chamber (Shuttle

0T-MRI-Side Railway Shuttle bed - PET and MRI scanners placed and

transfer the patients between the scan rooms Courtesy of GUMS

Optical Fiber Severe shielding of the PET components Imperfect

7 Gachon PET/MRI (Concept) Gachon PET/MRI (Implementation) Magnetic shielding Cho ZH et al. (Proteomics, 2008) HRRT-PET-Side Railway Middle Chamber (Shuttle Bed) 7.0T-MRI-Side Railway Shuttle bed - PET and MRI scanners placed and operated independently in neighboring rooms - Shuttle bed system to transfer the patients between the scan rooms Courtesy of GUMS Limitations in the PMT-based PET/MRI Simultaneous PET/MRI using Optical Fiber Severe shielding of the PET components Imperfect shielding separation of the scanners Shao Y et al., Phy Med Biol, 1997 PET Longer total scan time than PET/CT Reduction of patient throughput Courtesy of Philips MRI Kobe City University (Dr. Yamamoto) 7

8 U Cambridge & Siemens Energy spectra without (A) and with fiber optical bundle (B) : 90% light loss Energy resolution = 15% Energy resolution = 50% 30 mt micropet-mr system (Lucas et al., 2006) Yamamoto et al., Phy Med Biol, 2004 Decreased spatial resolution Low energy resolution Increased scatter & random Decreased NECR Semiconductor 8

Semiconductor Detector Avalanche Photodiode (APD) Visible & near-infrared light, Radiation (X or γ) p-n Junction Scintillation photon -V p type n type Entrance Window Cathode

Ionizing radiation can interact with the semiconductor material to form electron/hole pairs.

I r (spectrometers) ~ 300 um Doped Silicon Wafer h e - Signal 20 09 Avalanche Photodiode (APD) Avalanche Photodiode (APD) Scintillation photon ~ 300 um Doped Silicon Wafer Entrance

9 Semiconductor Detector Avalanche Photodiode (APD) Visible & near-infrared light, Radiation (X or γ) p-n Junction Scintillation photon -V p type n type Entrance Window Cathode Depletion Region - When reversely biased, a depletion region will be created near the p-n junction. Ionizing radiation can interact with the semiconductor material to form electron/hole pairs. The reverse current I r increases whose magnitude is directly proportional to the absorbed radiation energy. I r (spectrometers) ~ 300 um Doped Silicon Wafer h e - Signal Avalanche Photodiode (APD) Avalanche Photodiode (APD) Scintillation photon ~ 300 um Doped Silicon Wafer Entrance Window h h h h h h e - e- e e - - e - e - -V Cathode Advantages of APD Insensitivity to the magnetic field Compact size: high resolution application High quantum efficiency Courtesy of Siemens Medical System Signal LSO-APD PET-MRI System (U of Tübingen) APD PET/MRI (U of Tübingen) Judenhofer, Pichler et al (JOR, 2008) All nonmagnetic components & optimized detector/electronics Judenhofer, Pichler et al (JOR, 2008; Nature, 2008) 9

10 APD-based Brain PET Insert Siemens WB PET/MRI Courtesy of Herzorg H Self-shield 3T MRI PET Insert Siemens APD PET/MRI installed in Jülich, Germany Schwaiger M et al. (2005) 10

Radioisotopes and PET

Radioisotopes and PET 1 Radioisotopes Elements are defined by their number of protons, but there is some variation in the number of neutrons. Atoms resulting from this variation are called isotopes. Consider