Nuclear Medicine Imaging V Overview Nuclear medicine Therapeutic

Nuclear Medicine Imaging V.

Overview • Nuclear medicine: Therapeutic and diagnostic use of radioactive substances • Radioactivity: • Naturally occurring radioisotopes (radioactive isotopes) discovered 1896 by Becquerel • First artificial radioisotopes produced by the Curies 1934 (32 P) “Radioactivity, ” “Radioactive” • 1947 - Kohman: “Radionuclide” = nucleus of measurable half-life • 1935 - Hevesy uses 32 P for metabolic studies with Geiger-Muller counter • 1949 - First radionuclide imaging by Cassen of 131 I uptake in thyroid gland (scintillator+PMT, scanner, collimator, 1/4” spatial resolution) • 1957 - Anger camera (planar imaging) • 1960 - Kuhl & Edwards construct Mark IV scanner (~10 years before x-ray CT) • 1977 – Kayes & Jaszczak develop SPECT independently • 1950 – first PET attempts • 1976 – First commercial PET (Phelps & Hoffman at CTI) 9/26/2020 2

Radionuclide Imaging • Characteristics: • The distribution of a radioactive agent inside the body is imaged • Projection and CT imaging methods • Imaging of functional or metabolic contrasts (not anatomic) – Brain perfusion, function – Myocardial perfusion – Tumor detection (metastases) 9/26/2020 3

Nuclear Stability • The neutrons and protons which form the nucleus of an atom are held together by a combination of forces. Protons have alike charges and repel each other by the electrostatic force of repulsion. However, once the protons are put very close to each other an attractive force comes into play. This force is called the strong nuclear force, and is 100 times greater than the electrostatic force of repulsion. Neutrons are affected by a different weak nuclear force. The weak nuclear force causes neutrons to change spontaneously into protons plus almost massless nontinteracting particles called neutrinos. The gravitational force plays essentially no role in nuclear stability. • The laws of nuclear forces are very complex; the whole problem of analyzing the fundamental machinery behind nuclear forces is unsolved (Feynmann). • As a general rule, there about equal number of neutrons and protons in a nucleus. But, in heavier atoms, a greater proportion of neutrons have to be added to maintain the stability of the atom. 9/26/2020 4

Nuclear stability • The nucleus of many atoms is not stable. Nuclei with infavourable neutron/proton ratio will disintegrate or decay into stable nuclei by spontaneous emission of nuclear particles. • Example: electron Antineutrino (massless, neutral particle) neutron rich nucleus : proton rich nucleus : Positron neutrino Neutrino means “little neutral particle” in Italian. 9/26/2020 5

Nuclear Stability Neutron rich unstable element Proton rich unstable element 9/26/2020 6

Nuclear Stability • Nuclei tend to be most stable if they contain even numbers of protons and neutrons, and least stable if they contain an odd number of both. 9/26/2020 Number of protons Number of neutrons Number of stable nuclei Even 165 Even Odd 57 Odd Even 53 Odd 6 7

Definitions • Isotope: Nuclides of same atomic number Z but different N (and A) same element • Nuclide: Species of atom characterized by the constitution of its nucleus (in particular N, Z) • Radionuclide: Nuclide of measurable half time • Radioactive decay : the process by which an unstable nucleus is transformed into a more stable daughter nucleus by emitting nuclear particles. • Isomeric decay: If a nucleus gains stability by transition of a neutron between neutron energy levels, or a proton between proton energy levels, the process is termed an isomeric transition. In an isomeric transition, the nucleus releases energy without a change in its number of protons (Z) or neutrons (N). The initial and final energy states of the nucleus are said to be isomers. • Electron capture: Absorbtion of an extranuclear electron into the nucleus. • Decay scheme: depiction of nuclear mass energy plotted against the atomic number of the nuclei. 9/26/2020 8

Examples of Radioactive Decay 9/26/2020 9

Decay Schemes 9/26/2020 10

Examples: • -decay: 9/26/2020 Decay scheme (Hendee) 11

• Positron decay: • Electron capture: Decay scheme 9/26/2020 12

• Negatron decay: Decay scheme 9/26/2020 13

Competing processes of negatron emission, positron emission and electron capture 9/26/2020 Decay scheme 14

• Isomeric transitions after negatron decays Decay schemes 9/26/2020 15

Nuclear Activity • Radioactive decay is described by 99 m. Tc • N(t), N 0: number of radionuclide at time t = 0 and t, respectively. • : decay constant [1/t] • Activity A = average decay rate [decays per second] • Nuclear activity is measured in curie: 1 [Ci] = 3. 7 1010 decays/sec (originated from the activity of 1 g of 226 Ra) • Practical: 1 m. Ci, Ci. SI unit is becquerel [Bq] = 1 decay/second 9/26/2020 16

Interaction of Nuclear Particles and Matter • Alpha particles • Helium nucleus (4 He++), mostly occurring for parent with Z > 82 • ~ 3 -9 Me. V (accounts for the kinetic energy of the alpha particle + kinetic energy of the product nucleus) • + 2 charge large mass strong interaction (ionisation: attracts electrons from other atoms which become cations) • Poorly penetrating type of radiation (can be stopped by a sheet of paper). • Beta particles • Causes Bremsstrahlung (white, characteristic) • “Wiggly” motion in matter (low mass) • Gamma rays • Electromagnetic waves produces in nuclear processes ( < 0. 1 nm, E > 10 ke. V) • Identical to x-ray interaction (for E > 1. 02 Me. V: pair production and photo disintegration [emission of alpha, n, or p from nucleus]) 9/26/2020 17

Radionuclides in Clinical Use • Most naturally occurring radioactive isotopes not clinically useful (long T 1/2, charged particle emission) • Artificial radioactive isotopes produced by bombarding stable isotopes with high-energy protons or charged particles • Nuclear reactors (n), charged particle accelerators (Linacs, Cyclotrons) 9/26/2020 18

Radionuclide Generator • On-site production of • 99 m. Tc ke. V) 9/26/2020 99 m. Tc is the single most important radionuclide in clinical use (gamma @ 140 19

Radiopharmaceuticals and their uptake in the body In nuclear medicine imaging a radioactive isotope is introduced into the particular part of the body which is to be investigated. Ex: in order to follow heart, introduce the activity into the blood stream. Ex: In order to follow tyroid gland, introduce radioactive iodine (as tyroid absorb iodine) In some cases, neither of the two methods are possible. attach the radioactive subtance to another chemical which is chosen because ıt is preferentially absorbed by part of the body. The chemicals to which radipactive labels are attached are called radiopharmaceuticals. 9/26/2020 20

Radiopharmaceuticals (cont. ) If a chemical compound has one or more of its atoms substituted by a radioactive atom then the results is a radiopharmaceutical. For more detailed information: see Belcher & Velter “Radionuclides in medical diagnosis”, 1971 Selection of isotopes: 1) choose an isotope so that the resultant radiopharmaceutical is in the correct chemical form which will allow it to be absorbed by the particular organ to be imaged. 2) the energy of radiation must be suitable to the detectors to be used. Optimum energy range for gamma cameras is 100 -300 ke. V. Efficiency drops beyond this range 9/26/2020 21

Selection of isotopes (cont. ) 3) T 1/2 must not be too short, otherwise it will decay before the radiopharmaceutical can be delivered. It must not be too long, otherwise the patient will be unnecessarily exposed to ionization. T 1/2 (ideal) is a few hours. Exception: Se is used for pancreas scanning. T 1/2 is 120 days. 4) radiation dose delivered to patient must be as low as possible 5) radiopharmaceutical must be available, it should be cheap. The radionuclide that fulfills most of the above criteria is Technetium _ 99 m (99 m Tc), which is used in more than 90% of all nuclear medicine studies. 9/26/2020 22

Properties of 99 m. Tc: • T 1/2 = 6 h • radiates 140 ke. V gamma ray • the short half time and absence of Beta emission allows low radiation dose to patient. • The 140 ke. V gamma radiation allows for 50% penetration of tissue at a thickness of 4. 6 cm. Applications: • 99 m. Tc-Sestamibi • (myocardial perfusion, cancer) 99 m. Tc-labeled hexamethyl-propyleneamine (brain perfusion) Other gamma emitters: 123 9/26/2020 I, 111 In, 67 Ga, 201 Tl, 81 Kr m 23

Positron emitters: • 11 C , T 1/2 = 20 min – many organic compounds (binding to nerve receptors, metabolic activity) • 13 N , T 1/2 = 10 min – NH 3 (blood flow, regional myocardial perf. ) • 15 O , T 1/2 = 2. 1 min – CO 2 (cerebral blood flow), O 2 (myoc. O 2 consumption), H 2 O (myoc. O 2 consumption & blood perfusion) • 18 F, T 1/2 = 110 min – 2 -deoxy-2 -[18 F]-fluoroglucose (FDG, neurology, cardiology, oncology, metabolic activity) 9/26/2020 24

Imaging As long as the photons emanating from the radionuclide have sufficient energy to escape from the human body in significant numbers, images can be generated that portray in vivo distribution of the radiopharmaceutical. Nuclear medical imaging may be divided into three categories: 1) conventional or planar medical imaging, 2) Single photon emission computed tomography (SPECT), 3) Positron emission tomography (PET). 9/26/2020 25

Conventional or planar imaging The three-dimensionally distributed radiopharmaceutical is imaged onto a planar or two-dimensional surface producing a projection image. 9/26/2020 26

A single detector system for rectilinear scan 9/26/2020 27

Image formation • A scanning mechanism makes a rectilinear motion above the patient. • The collimator ensures that each small part of the crystal views only a small area of the organ to be imaged. • Gamma rays which pass through a hole in the collimator must interact in the crystal immediately behind that hole. • The electrons involved in the interaction of the gamma ray with the crystal are stopped very close to the point of interaction and hence the scintillations produced originate very close to the point of interaction. • Each gamma ray which interacts in the crystalis called ‘ an event ’. • Many events in the crystal produce a scintillation image. • Each event must be processed independently to locate the origin of the scintillations for that event, i. e, the point of interaction of the gamma ray. This is accomplished by the PM tube array and associated electronics. 9/26/2020 28

• The light scintillations are detected by the PM tube array with the PM tube closest to the origin of the scintillations detecting the most light. • Other PM tubes, further from the origin of the scintillations, will detect lesser amounts of light. • The light detected by each PM tube is proportional to its proximity to the origin of the scintillations. • Each PM tube converts the light detected to a electron pulse. The amplitude of this pulse is proportional to the intensity of the light the particular PM tube detects, i. e, it is related to the proximity of the PM tube to the point of interaction. • Each event is ‘located’ using information from all the PM tubes and finally • the position circuitry processes this information and can locate the point of interaction to within 2 -3 mm 9/26/2020 29

Detection of Gamma Radiation • Scintillation detectors are the most commonly used detectors: • Crystals: Na. I(Tl) (thallium-activated sodium iodide) , BGO (Bismuth Germanate), Cs. F, Ba. F 2 (Barium Fluoride) • Criteria: Stopping power, response time, efficiency, energy resolution • Other methods, like ionization chambers and semiconductor detectors can also be used. 9/26/2020 30

Pulse Height Analyzers (PHA) 9/26/2020 31

Pulse Height Analyzers • In NM imaging the pulse height analyser (PHA) is the main component used to reject scatter. • Any gamma-rays which have scattered in the body will strike the crystal and deposit less than the full energy in the crystal. • Most of these events can be rejected by the PHA. • Only those events corresponding to unscattered gamma-rays are used to form the image. • Note that the rejection is not perfect but without the PHA the NM image would be almost useless particularly for large subjects where scatter is very significant 9/26/2020 32

Scintillation Camera (Anger Camera) • Imaging of radionuclide distribution in 2 D • Replaced “Rectilinear Scanner”, faster, increased efficiency, dynamic imaging (uptake/washout) • Application in SPECT and PET • One large crystal (38 -50 cm Dia. ) coupled to array of PMT 1. 2. 3. 4. 5. Enclosure Shielding Collimator NI(Ti) Crystal PMT 9/26/2020 33

Anger Logic The Anger camera is a system for achieving a large number of resolvable elements with a limited number of detectors. It thus overcomes the previous difficulty of having the resolution limited by the number of discrete detectors. The principle is based on estimating the position of a single event by measuring the contribution to a number of detectors. GAMMA-RAY PHOTON Cameras of this general type have a single crystal viewed by arrays of detectors SCINTILLATING CRYSTAL with the detected outputs followed by a position computer LIGHT PHOTONS to estimate the position of PHOTODETECTOR x 1 x 2 I 1 9/26/2020 x each event. I 1 x 1+ I 2 x 2 I 1+I 2 34

Applications Thyroid imaging: The thyroid gland is situated in the lower part of the neck at a depth of about 1 cm. The purpose of thyroid is to secrete the hormone thyroxin which is carried in the blood stream and controls a number of body functions: • stimulate metabolism • influence growth • control mental development • store iodine underactive thyroid : • mental dullness, • low temperature 9/26/2020 • decrease in metabolism 35

Imaging of thyroid can be useful for the following purposes: 1. To determine the amount of thyroid tissue left after surgery or radiotherapy for thyroid disease, 2. To detect thyroid metastases associated with thyroid cancer, 3. To show the comparative function of different parts of the glands, 4. To measure the size and position of the thyroid prior to surgery or other treatments of the disease. 9/26/2020 36

• Iodine is trapped in the thyroid. • Approximately, 20 -30% of ingested iodine concentrates in the normal thyroid. • Previously used imaging. 131 I (the most readily available iodine isotope) for thyroid • However, 131 I has unsuitable properties for NM imaging, i. e. , *long half-life *emits beta-particles *emits high energy (364 ke. V) gamma rays. 9/26/2020 37

• • 123 I has a half-life of 13. 3 hr and emits gammas of energy 159 and 28 ke. V. 123 I is possibly the best radionuclide of iodine for imaging but it is expensive and not readily available. • The pertechnetate ion (Tc. O 4) also concentrates in the thyroid. It can also be trapped in the thyroid. • About 2 -3 % of IV administered Tc. O 4 concentrates in the normal thyroid which is sufficient for imaging. • 120 MBq of Na 99 m. Tc. O 4 is administered IV and images are obtained 15 min later. 9/26/2020 38

Normal image: • uniform distribution throughout both lobes • the isthmus is well defined Abnormal image: • GRAVE’S DISEASES increased uptake and general enlargement of the gland. • TUMOUR usually ‘cold’ spots and the gland is distorted but may be carcinoma, adenoma or cyst ‘hot’ spots (particularly singular hot spots) are generally benign 9/26/2020 39

• Lung Imaging: • INDICATIONS * suspected pulmonary emboli (PE) * malignancy * emphysema (excess air in lungs) • PROCEDURE FOR VENTILATION IMAGE * the patient is positioned for imaging and breathes technegas which is carbon particles labelled with 99 m. Tc Inhalation continues until a predetermined count rate is obtained then * multiple views are obtained * the system is then opened to clean air and the “active” material washes out from the lungs fairly quickly. 9/26/2020 40

The perfusion image: • 120 MBq of 99 m. Tc labelled MAA (macroalbumin agregate) is administered IV with the patient supine. • MAA are 10 -30 m in size and lodge in the capillaries of the lung. • about 200, 000 particles of MAA are administered and block ~ 1 in 1000 capillaries. • they are biodegradable. • T 1/2(biol) =6 - 9 hr. • the same views as for the ventilation scan are obtained with the patient supine 9/26/2020 41

• PE detected in the NM image will show little or no radiographic change on a plain x-ray • NM imaging for PE is * safe * simple, and * very sensitive • the pulmonary angiogram is the ‘gold standard’ for diagnosis of PE • however it is * expensive * invasive * involves some risk and * is used only when the NM image is inconclusive 9/26/2020 42

Imaging kidney cortex: • use 150 MBq of 99 m. Tc-DMSA or GHA • these pharmaceuticals localise in the renal cortex • generally used in combination with an IVP and ultrasound 9/26/2020 43

Single Photon Emission Computed Tomography (SPECT) • If one or more gamma cameras are attached to a computer controlled gantry, which allows the detectors to be rotated around a patient, multiple views (or 2 D projections) of the 3 D pharmacutical distribution can be acquired. • First SPECT 1963 (Mar IV) used array of detectors • Rotation, Translation • High count rates • Many components • Mostly single-slice • Rotating camera: • Multiple slices • Multi-camera systems 9/26/2020 44

Collimators for SPECT Collimator restricts the acceptance angle Geometry 9/26/2020 45

SPECT Artifacts • Reconstruction methods similar to x-ray CT • Attenuation: gamma-ray originating from the source is attenuated by tissue. Two unknowns: 1)concentration of tracer, and 2) distribution of tissue attenuation coefficients. • Corrective measures: 1) Transmission measurement with external source to determine tissue absorbtion 2) Assume constant absorption and use geometric mean of two measurements 180 apart, which is independent on d 3) Iterative reconstruction 9/26/2020 46

Using the Geometric Mean Let there be an activity A at depth d from detector I. Assume that the object has a constant attenuation coefficient. Then the fraction of photons reaching that detector (C 1) is proportional to e- x, that is Survival probability 9/26/2020 47

Geometric mean (cont. ) The fraction of photons reaching the second detector (C 2) is: If the geometric mean is used, then which is totally independent of source depth. Provided an outline of the body, a simple correction can be applied to the combined opposed projections. 9/26/2020 48

Iterative Reconstruction method 9/26/2020 49

The image domain can be discretized and acquired ray sums can be expressed by: where Ai : activity contained in the ith voxel, p (k) : projection data at angle , the sum of weighted activity (or ray sum) along the kth ray at angle of view , fi k, : fractional volume of the ith element that is contained within the kth ray, i : the attenuation coefficient of the ith element (corresponding to the energy of the photon), lj k, : length of the portion of the kth ray that is contained within the ith element 9/26/2020 50

exp(- j lj k, ) : attenuation factor for radiation originating from the ith element. The index j denotes elements lying along the kth ray between the ith element and the boundary of the object nearest the detector. Iterative method • Assume attenuation distribution, find Ai • Calculate attenuation distribution using Ai • Find new estimate for Ai using the calculated attenuation coefficients, 9/26/2020 51

Positron Emission Tomography • Use with positron emitters (beta-plus) • Positron annihilates with electron of nearby atom two gamma quanta each at 511 ke. V leave under 180 • “Tagging” of radiation: • Windowing • Coincidence detection (“electronic collimation”) 9/26/2020 52

PET Detectors • Individual Coupling: Expensive, packing problematic, high count rate • Block Design: Digital encoding, longer dead time, more economic, somewhat reduced resolution 9/26/2020 53

PET Resolution compared to MRI • Modern PET ~ 2 -3 mm resolution PET MRI 9/26/2020 54

Functional Imaging 9/26/2020 55