Nuclear Imaging in the Realm of Medical Imaging

Nuclear Imaging in the Realm of Medical Imaging Frank Deconinck Nuclear Medicine, Vrije Universiteit Brussel Laarbeeklaan 101, B-1090 Brussels, Belgium frank. deconinck@vub. ac. be 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 1

Medical imaging is … In medical imaging, particular physical characteristics of the body are mapped in an image. Examples: • to map temperature in thermography we detect IR radiation • in CT, attenuation of X-rays maps electron density • reflection of ultrasound is due to differences in acoustical impedance • nuclear imaging shows tracer uptake 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 2

Thermography • Thermography maps temperature 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 3

An image is … An image is the projection of particular characteristics of an object on a map with a dimensionality which is typically lower than that of the object. A patient is 4 D: 3 D in space, 1 D in time. A typical image will be 2 D in space (static) or 2 D in space and 1 D in time (dynamic). 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 4

Information flow Information about the patient has to be detected by adequate imaging equipment (‘imager’), shown in an image and observed by an observer. There is information flow: patient imager image observer 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 5

Patient imager image observer Information flow implies information carriers: • • sound waves in ultrasound radio waves in MRI X-rays in CT � -rays in nuclear imaging The information carriers interact with their environment, e. g. • sound waves will be refracted, reflected and absorbed • -rays will be absorbed and scattered. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 6

Spectrum of techniques 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 7

Medical imaging techniques • Ultrasound • MRI (magnetic resonance imaging) • Radiology … • Planar nuclear imaging • Tomographic nuclear imaging – Single Photon Emission Computed Tomography (SPECT) – Positron Emission Tomography (PET) 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 8

Ultrasound 1970 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 9

Information in ultrasound Sound waves: – Reflection, function of acoustic impedance – Refraction, function of index of refraction – Absorption and scattering 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 10

Ultrasound 1990 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 11

2 D/3 D ultrasound 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 12

4 D Ultrasound 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 13

US scanner 1954 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 14

US scanner 2002 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 15

MRI 1981 -1983 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 16

Information in MRI • Magnetisation of hydrogen nuclei (spins): N(H) • Energy transfer between spins and tissue: T 1 • Energy transfer among spins: T 2 • flow 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 17

MRA 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 18

2 -D / 3 -D MRI 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 19

NMR Aberdeen 1979 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 20

MRI scanner 2002 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 21

Rx - Roentgen 1895 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 22

Information in radiology X-ray attenuation through – Absorption – Scattering Proportional to – Number of electrons along X-ray path (projection radiology) – Electron density (CT) Physics: photon/matter interactions 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 23

Rx - planar 2000 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 24

Rx film / digital detector GE Cs. I scintillator + amorphous Si readout 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 25

Rx - first CT 1972 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 26

Rx - CT 2000 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 27

Rx - first CT scanner 1972 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 28

CT scanner 2002 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 29

Planar nuclear imaging, 1957 (g-camera Hal Anger) 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 30

Information in nuclear medicine The distribution of a radiotracer (a radioactive biologically active substance) in space and/or time. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 31

Planar nuclear imaging, 2001 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 32

g-camera, Hal Anger , 1957 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 33

SPE(C)T, 1968 (David Kuhl) SPE(C)T = Single Photon Emission (Computed) Tomography 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 34

SPECT, 1999 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 35

SPECT camera 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 36

PET 1981 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 37

PET 2002 Courtesy U. Noelpp, Univ. of Bern 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 38

PET camera 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 39

CT-PET camera 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 40

Tracers • A radioactive biologically active substance is chosen in such a way that its spatial and temporal distribution in the body reflects a particular body function or metabolism. • In order to study the distribution without disturbing the body function, only traces of the substance are administered to the patient. • The radiotracer decays by emitting gamma rays or positrons (followed by annihilation gamma rays). • The distribution of the radioactive tracer is inferred from the detected gamma rays and mapped as a function of time and/or space. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 41

Tc-99 m decays by emitting a 140 ke. V gamma ray. Its half life is 6 hours. – The -rays can be detected and the original tracer distribution directly visualised as projections by means of a gamma camera; – By measuring projections over an adequate set of angles (π or 2π), tomographic reconstructions can be performed to generate images of the tracer distribution in virtual slices through the body. Tc-99 m is used in more than 90% of all ‘single photon’ nuclear medicine studies. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 42

Example of Tc-99 m scan 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 43

F-18 decays by emitting a positron – The positron travels in tissue for < 1 mm before colliding and annihilating with an electron; – The rest energy of the particles (the energy equivalent to the mass of both electron and positron: E=mc 2 x 2) is liberated in the form of two oppositely directed (space) coincident (time) gamma rays of 511 ke. V. – By detecting a large number of coincident photons over a 2π geometry, tomographic reconstruction techniques yield images of the original tracer distribution. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 44

Example F-18 scan 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 45

Tomographic reconstructions Filtered backprojection 03/12/2020 Iterative reconstruction Nuclear Imaging, Amsterdam, September 8 -12 2002 46

Example backprojection 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 47

Filtered backprojection For the slice at level y: 1. Take line y of the projection image at acquisition angle f; 2. Smear line out (= backproject) in new image (which will become the tomographic slice image) along angle f; 3. Do so for all angles and add all backprojected images to the previous ones; 4. Sum is a blurred image in which each point source has become a 1/r function; 5. Sharpen image by deconvolution of 1/r (‘ramp’ in Fourier domain). 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 48

Example iteration Example: calculate square root of 200 (should be 14, 14). 1. 2. 3. 4. 5. 6. 7. First estimate 10: divide 200/10 = 20; Mean of 10 and 20 = 15: new estimate Divide 200/15 = 13, 33; Mean of 15 and 13, 33 = 14, 16: new estimate; Divide 200/14, 16 = 14, 12 Mean of 14, 16 and 14, 12 is 14, 14 Divide 200/14, 14 = 14, 14 : stable result obtained after 3 converging iterations. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 49

Iterative reconstruction 1. Start from any image estimate; 2. Calculate projections which would have been acquired using the estimated image as a virtual object; 3. Compare with actual data and calculate difference; 4. Backproject difference to generate corrected image estimate 5. Go back to 2. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 50

Historical milestones • de Hevesy and Paneth, 1923: Pb in plants • de Hevesy and Chiewitz, 1935: P-32 in rats • Ziedses des Plantes, 1950, and Cassen, 1951: rectilinear scanner • Brownell, 1951: positron imaging • Anger, 1957, gamma-camera • Kuhl, 1963, emission tomography • Muehllehner, 1971, positron tomography • Keyes, 1977, SPECT 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 51

Henri Becquerel 1896 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 52

de Hevesy, 1935 On P-32 uptake in rats: “This result strongly supports the view that the formation of bones is a dynamic process, the bone continuously taking up phosphorus atoms which are partly or wholly lost again, and are replaced by other phosphorus atoms” 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 53

Thank you 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 54

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Limiting factors patient imager image observer • • Patient: attenuation, movement, … Imager: hard/software, artefacts, … Image: noise versus resolution Observer: training, bias, … 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 56

Image: noise Statistics (k) and lesion contrast (C) determine the number of lesions (T) which can be seen in a noisy image containing N photons: T=(NC 2)/k 2 (Rose) 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 57

Image processing • • Data correction Image enhancement Image analysis Information display 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 58

Gamma camera processing and display electronics PM's crystal collimator (pinhole) Hal Anger, 1956 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 59

Collimator No lenses exist for X- or -rays. To form a -ray image on the detector plane, one has to use either a pinhole collimator (camera obscura principle) or a multihole collimator. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 60

Photon detection The detection of the photons is based on the transfer of their energy to the detector through the photo-electric and the Compton effect. Examples are – Scintillators, e. g. Na. I, BGO and LSO (cfr. talk by C. van Eijk) – Semiconductor detectors, e. g. Si, Ge – Gas detectors, e. g. with a wire chamber read-out (MWPC, HIDAC, …) 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 61

Scintillator In the scintillator detector, the energy of an absorbed -ray -E - is transformed into an equivalent starlike shower of N scintillation photons, in which each scintillation photon has an energy Escint, such that E = NEscint. Those scintillation photons can be detected by photomultipliers (PM’s) (or photodiodes). 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 62

Na. I crystal 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 63

Detector and PM’s Detector size up to 60 x 40 cm (single crystal); up to 100 PM’s. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 64

Energy and location The energy of the incoming rays is checked by means of the total number of detected photons. If the total number is either too low or too high, the event is discarded. Typical energy resolution is 10%. The location of accepted events is determined by weighing the contribution of the light measured by different PM’s at known locations. Typical ‘intrinsic’ spatial resolution is 5 mm. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 65

The projection scintigram The image thus obtained is a projection in which each picture element (pixel) is incremented by one each time a -ray is detected at the location of the pixel. Typical images will contain (order of magnitude) 106 photons, distributed over 1282 pixels, i. e. between 10 and 1000 photons per pixel (±√N !). The resulting ‘system’ spatial resolution is typically 10 mm. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 66

SPECT By rotating the camera around the patient and measuring projection images over an adequate set of angles (e. g. 64 over 2π), the distribution of the tracer can be calculated in virtual slices through the body using tomographic reconstruction algorithms. This improves the detectability of lesions if the original projection data contain enough information (S/N ratio high enough). 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 67

Positron camera 1/2 In positron-electron annihilation, two 511 ke. V rays are emitted simultaneously (‘coincidentally’) in opposite directions. When two opposed detectors simultaneously detect those two rays, one knows that a positronelectron annihilation has occurred along the line connecting the two detectors. Typical geometric configurations are ring or opposed planar detectors 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 68

Positron camera 2/2 • Geometry (ring with/without septa, opposed planar detectors) : sensitivity • Dead time: loss of data, noise, saturation • Coincidence window (true versus accidental events, contrast) : dead time, contrast, noise • Co-linearity and positron range: blurring 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 69

Ring geometry 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 70

Patient: attenuation The half-value layer (50% attenuation) for 140 ke. V photons in soft tissue is 44 mm. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 71

Imager: hard/software, artefacts, … • Slide, courtesy of David Townsend, CT-PET 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 72

Radioactive decay A nucleus is unstable and will return to a more stable state through radioactive decay when – The nucleus is in an excited energy state, e. g. Tc-99 m: emission of a -ray. – There is an unbalance between the number of protons and neutrons • �b- decay, e. g. C-14: emission of an electron • �b+ decay, e. g. F-18: emission of a positron (the positron is the antimatter of the electron: same mass but opposite charge) • Electron capture, e. g. Tl-201: emission of characteristic X-rays • a-decay, e. g. Rn-222: emission of a He nucleus – Its total mass is too large: fission, e. g. U-235 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 73

Reflection of sound waves Acoustic impedance Z = x v = density (typically 1000 kg/m 3) v = speed of sound (typically 1500 m/s) Reflected fraction at tissue boundaries: – Muscle fat: 0, 011 – Muscle air: 0, 999 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 74

Origin of MRI signal • Put spins in a large external magnetic field: spins orient parallel (lowest energy) or anti-parallel (highest energy); • Energy difference E=h ; for a field B=1, 5 T, =60 MHz (radio waves); • Irradiate tissue with radio wave pulse at resonance frequency =60 MHz to excite spins (flip them from parallel to anti-parallel); • Spins flip back and emit radio waves at frequency ; • Detect radio waves. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 75

Photon/matter interactions • Photo-electric effect: the energy of the photon is transferred to an electron. The photon disappears. • Compton scattering: part of the energy of the photon is transferred to a ‘free’ electron. The photon changes direction and its energy decreases. • Coherent scattering: not relevant for imaging • Pair formation: not relevant for imaging 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 76

Photo electric effect The incident photon disappears ! 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 77

Compton effect Part of the energy of the photon will be transferred to a ‘free’ electron. The photon will change direction and its energy will decrease. 03/12/2020 Nuclear Imaging, Amsterdam, September 8 -12 2002 78