Nuclear Medicine Physics Module Lecture Notes (PDF)

Nuclear Medicine Physics Module Dr Mohammed Saeed Alqahtani Lecture 1: Introduction Welcome Back  2 Our agreement I wish all students arrived on time, and for those who came late.. PLEASE find your place with minimal disturbance for your fellow students. Do ask questions at anytime.. during the lec...

Nuclear Medicine Physics Module Dr Mohammed Saeed Alqahtani Lecture 1: Introduction Welcome Back  2 Our agreement I wish all students arrived on time, and for those who came late.. PLEASE find your place with minimal disturbance for your fellow students. Do ask questions at anytime.. during the lectures or the practical sessions Give yourself enough time to read and understand your notes, and let’s discuss any potential problem that you may face ASAP 3 Introduction  The technologies used in nuclear medicine for diagnostic imaging have improved over the last century, starting with Röntgen’s discovery of X rays and Becquerel’s discovery of natural radioactivity.  Each decade has brought innovation in the form of new equipment, techniques, radiopharmaceuticals, advances in radionuclide production and, ultimately, better patient care.  All such technologies have been developed and can only be practised safely with a clear understanding of the behaviour and principles of radiation sources and radiation detection. 4 Radioactivity 5 Stable nuclei  Nearly, all the nuclides extant in the world are stable. Apart from the nucleus of ordinary hydrogen, which consists of a single proton, all the stable lighter nuclei contain nearly equal numbers of protons and neutrons. For example: Helium atom 6 Isotopes  Isotopes of an element are nuclides that have the same number of protons (atomic number), position in the periodic table, and chemical and metabolic properties, but a different number of neutrons, mass number (protons + neutrons), density and other physical properties. 7 Isotopes For example: (Carbon-12)  stable  6 neutrons + 6 protons 14C (Carbon-14)  unstable  8 neutrons + 6 protons (a neutron excess) 11C (Carbon-11)  unstable  5 neutrons + 6 protons (a neutron deficit) 12C  Both 14C and 11C are artificially produced, unstable and radioactive. 8 Radionuclides  Unstable nuclei are radioactive and decay until they become stable nuclei with the emission of any combination of alpha, beta and gamma radiation.  Naturally occurring radionuclides, such as uranium, radon and radium, contribute to our background radiation exposure, whether external to the body or internal. 9 Production of radionuclides  There are more than 2700 known radionuclides.  Radionuclides used in medical imaging are produced artificially, in the following ways: 10 Production of radionuclides A) If an additional neutron is forced into a stable nucleus  a neutron excess  This process occurs in a nuclear reactor. For example, with Molybdenum: 98Mo +n 99Mo  The atomic number of the nucleus remains unchanged, but its mass has been increased by one. 11 Production of radionuclides B) If an additional proton is forced into a stable nucleus, knocking out a neutron  a neutron deficit  This process occurs in a cyclotron, which accelerates positively charged ions (protons, deuterons or alpha particles) on the target material. For example, with oxygen: 18O +p 18F +n  The mass number has not been changed, but its atomic number has increased by one to become fluorine. 12 Production of radionuclides  Radionuclides produced in a cyclotron are short-lived (i.e. with half-lives ranging from less than a minute to a couple of hours).  So, it is only possible to use them reasonably close to the cyclotron.  Medical minicyclotrons have been designed specially for the production of short-lived radionuclides such as fluorine-18 (18F) at or near the hospital site. 13 Production of radionuclides Cyclotron 14 15 Nuclear Medicine Physics Module Dr Mohammed Saeed Alqahtani Lecture 2 Production of radionuclides  There are more than 2700 known radionuclides.  Radionuclides used in medical imaging are produced artificially, in the following ways: 2 Production of radionuclides A) If an additional neutron is forced into a stable nucleus  a neutron excess  This process occurs in a nuclear reactor. For example, with Molybdenum: 98Mo +n 99Mo  The atomic number of the nucleus remains unchanged, but its mass has been increased by one. 3 Production of radionuclides B) If an additional proton is forced into a stable nucleus, knocking out a neutron  a neutron deficit  This process occurs in a cyclotron, which accelerates positively charged ions (protons, deuterons or alpha particles) on the target material. For example, with oxygen: 18O +p 18F +n  The mass number has not been changed, but its atomic number has increased by one to become fluorine. 4 Production of radionuclides  Radionuclides produced in a cyclotron are short-lived (i.e. with half-lives ranging from less than a minute to a couple of hours).  So, it is only possible to use them reasonably close to the cyclotron.  Medical minicyclotrons have been designed specially for the production of short-lived radionuclides such as fluorine-18 (18F) at or near the hospital site. 5 Production of radionuclides Cyclotron 6 Production of radionuclides C) Radioactive fission products may be extracted from the spent fuel rods of nuclear reactors 238U  99Mo + other fission by-products  As the molybdenum is different chemically from the other products, it can be separated and prepared in a very pure form. 7 Production of radionuclides D) Some radionuclides are daughter products obtained from generator that contain a longer-lived radioactive parent.  Useful daughter products: Molybdenum-99 (99Mo) generator  Technetium-99m (99mTc) Germanium-68 (68Ge) generator  Gallium-68 (68Ga) 8 Radioactive transformation (Decay) 9 Radionuclides with a neutron excess (β- decay)  Radionuclides with a neutron excess may lose energy and become stable by a neutron changing into a proton plus an electron.  The electron is ejected from the nucleus with high energy and is referred to a negative beta particle n  p + β- 10 Radionuclides with a neutron excess (β- decay) For example: Iodine-131 (131I) with atomic number 53, decays in this way to xenon-131 (131Xe), with atomic number 54.  There has been no change of mass number, but the atomic number has increased by one. 11 Radionuclides with a neutron excess (β- decay)  Isomeric transition  in the case of some radionuclides, the gamma ray is not emitted until an appreciable time after the emission of the beta particle. For example: 99Mo decays by the emission of negative beta particle, the daughter nucleus technetium remains in the excited state for a variable length of time, which averages a matter of hours. - It is said to be metastable and is written as 99mTc 12 Radionuclides with a neutron excess (β- decay) Parent nuclide  emission (half-life) daughter nuclide  99mTc decay to the ground state, technetium-99 (99Tc), and the decay happens with the emission of a gamma ray of energy 140 keV.  Both 99mTc and 99Tc are said to be isomer, nuclei having different energy states and halflives, but otherwise indistinguishable as regards mass number, atomic number and other properties. half-life = 6 hours  decay to 99Tc  unstable 99Tc half-life = 211000 years  decay to ruthenium-99 (99Ru)  stable 99mTc 13 Radionuclides with a neutron excess (β- decay) 14 Radionuclides with a neutron deficit: β+ decay or K-electron capture β+ decay  Radionuclides with a neutron deficit may lose energy and become stable by a proton within the nucleus changing into a neutron and a positive electron.  The positive electron is ejected from the nucleus with high energy and is referred to a positive beta particle (i.e. positron) p  n + β+ 15 Radionuclides with a neutron deficit: β+ decay or K-electron capture  For example: Fluorine-18 (18F) with atomic number 9, transforms into oxygen-18 (18O), with atomic number 8.  There has been no change of mass number, but the atomic number has decreased by one. 16 Radionuclides with a neutron deficit: β+ decay or K-electron capture K-electron capture  the nucleus may increase its number of neutrons relative to the number of protons by capturing an extranuclear electron from the nearest K-shell. p + e-  n  The daughter nuclide will emit K-characteristic X-rays when an electron from an outer shell fills the created in the K-shell. 17 Radionuclides with a neutron deficit: β+ decay or K-electron capture  For example: Iodine-123 (123I) decays wholly by electron capture and emits 160 keV gamma and 28 keV X-rays but no positive beta particles. 18 Gamma rays  The gamma rays emitted during radioactive decay of a given radionuclide have at most a few specific energies (forming a line spectrum) that are characteristic of the nuclide that emits them.  Gamma rays have identical properties to X-ray. 19 Gamma rays For example: Iodine-131 (131I) emits mostly 364 keV gamma rays. 20 Positron emitters  Positive electrons (i.e. positrons) have a very brief existence.  When a positive beta particle comes to the end of its range, it combines with a nearly negative electron.  The opposite charges neutralise each other.  The combined masses of the two electrons are wholly converted into energy. 21 Positron emitters  According to Einstein's formula (E = m c2 ) for the equivalence between energy E and mass m, the mass of each electron is equivalent to 511 keV.  When the positive and negative electrons annihilate each other, the energy is emitted as two photons of annihilation radiation (each of 511 keV) travelling in opposite directions.  Positron emitters are used in positron emission tomography (PET) imaging. 22 Positron emitters 23 Radioactive decay  Radioactive disintegration is a stochastic (random) process.  It is impossible to predict which of the unstable nuclei in a sample will disintegrate in the next second.  BUT it is possible to be quite precise about the fraction that will disintegrate on account of the large numbers of nuclei the sample contains. 24 Activity  A radioactive nucleus does not make its presence known until it decays and emits a beta or gamma rays, or both.  The quantity of radioactivity is measured not by the ‘population’, the mass or number of radioactive atoms, BUT by the transformation rate, i.e. the number that represents disintegrate per second (also known as the decay rate). 25 Activity  The activity of radioactive sample is the rate of disintegration, the amount of disintegrating per second.  The SI unit is the Becquerel (Bq) = 1 disintegration per second.  In medical gamma imaging, most radionuclide administrations are measured in megabecquerels (1 MBq = 106 Bq).  The activity of radionuclide generators in gigabecquerels (1 GBq = 109 Bq).  A unit found in old textbooks is the curie (Ci)  1 mCi = 37MBq 26 Activity  When the gamma rays enter a detector, they may be registered individually as counts.  The count rate [number of counts per second (cps)] measured by a given instrument is less than the activity, because the greater proportion of the rays usually miss the detector and some pass through it undetected. However, there is a proportionality: Count rate α activity α number of radioactive atoms in the sample 27 Activity  The fundamental law of radioactive decay states that the activity of a radioactive sample decreases by equal fractions (percentage) in equal interval time. This is referred to as the exponential law.  However long the time, the activity of a radioactive sample never falls to zero. 28 Physical half-life  The half-life (t1/2) of a radionuclide is the time taken for its activity to decay to half of its original value.  For example: * Two successive half-lives reduce the activity of a radionuclide by a factor of 2 X 2 = 4. * Ten half-lives reduce the activity by a factor of 210 ≈ 1000 29 Physical half-life what is the def with biological and Pusical Radioactive decay reduces the number of radioactive nuclei over time. In one half-life (t1/2), the number decreases to half of its original value. Half of what remains decay in the next halflife, and half of those in the next, and so on. This is an exponential decay, as seen in the graph of the number of nuclei present as a function of time. 30 Physical half-life  This half-life is more properly called the physical half-life.  It is a fixed characteristic of the radionuclide, cannot be predicted for a given radionuclide in any way.  The physical half-life is unaffected by any other factors, such as heat, pressure, electricity or chemical reactions.  It can range from fractions of a second (useless in imaging) to millennia in the case of 99Tc (also useless in imaging). 31 Physical half-life  Physical half-lives of some radionuclide used in medical imaging: Half-life - Half-life Radionuclide 67 h Molybdenum-99 Rubidium-82 - 67 h Indium-111 10 min Nitrogen-13 73 h Thallium-201 20 min Carbon-11 78 h Gallium-67 5 days Xenon-133 8 days Iodine-131 211 000 years Technetium-99 13 s D 1 min D 68 min 110 min 6h 13 h - Radionuclide Krypton-81m & Gallium-68 & Fluorine-18 Technetium-99m P Iodine-123 & > important on NM 32 Effective half-life  When a radionuclide is used in medical gamma imaging, it usually forms part of a salt or organic compound, the metabolic properties of which ensure that it concentrates in the tissues or organ of interest.  A pharmaceutical that has been labelled with a radionuclide is referred to as a radiopharmaceutical. 33 Effective half-life  If the pharmaceutical alone is administered, it is gradually eliminated from the tissue, organ and whole body by the usual metabolic processes of turnover and excretion.  Such a process can be regarded as having a biological half-life (tbiol).  If the radionuclide is stored in a bottle, its activity decays with its physical half-life (tphys). 34 Effective half-life  If the radiopharmaceutical is administered to a patient, the radioactivity in specific tissue, an organ or the whole body decreases because of the simultaneous effects of radioactive decay and metabolic turnover and excretion.  The radiopharmaceutical can be regarded as having an effective half-life (teff). 35 Effective half-life  The effective half-life is shorter than either the biological or physical half-lives. teff < tbiol , tphys 1/teff = 1/tbiol + 1/tphys  The effective half-life depends on the radiopharmaceutical used and the organ involved, and it can vary from person to person, depending on their disease state. 36 Radiopharmaceuticals 37 - Radiopharmaceuticals  Desirable properties of a radionuclide for imaging are as oh half-lif follow: the best Techa H 1. A physical half-life of a few hours, similar to the time from preparation to injection. If the half-life is too short, much more activity must be prepared than the actually injected. cuse have - 2. Decay to a stable daughter or at least one with a very long half-life (e.g. 99Tc has half-life of about 211000 years). S = contaminating 38 Radiopharmaceuticals  Desirable properties of a radionuclide for imaging are as follow: 3. Emission of gamma rays (which produce the image), but not alpha or beta particles nor very low energy photons, which have a short range in tissue and deposit unnecessary dose in the patient. 4. Emission of gamma rays of energy 50-300 keV and ideally about 150 keV – high enough to exit the patient but low enough to be easy collimated and easily detected. = looker 39 Radiopharmaceuticals  Desirable properties of a radionuclide for imaging are as follow: energy sing) Has 5. Ideally, emission of monoenergetic gamma rays, so that scattered radiation can be eliminated by energy discrimination with a pulse height analyser (PHA). sing 6. Easily and firmly attached to the pharmaceutical at room temperature, but has no affect on its metabolism. 40 Radiopharmaceuticals  Desirable properties of a radionuclide for imaging are as follow: 7. Readily available at the hospital site. 8. A high specific activity, i.e. high activity per unit volume. 41 Radiopharmaceuticals  Desirable properties of a radiopharmaceutical are as follow: 1. localise largely and quickly in the target (i.e. the tissue of interest) 2. be eliminated from the body with a effective half-life similar to the duration of the examination, to reduce the dose to the patient 3. have a low toxicity 42 Radiopharmaceuticals  Desirable properties of a radiopharmaceutical are as follow: 4. form a stable product both in vitro and in vivo 5. be readily available and inexpensive per patient dose  The decay during transport and storage of a short-lived radionuclide is reduced if it can be supplied with its longerlived parent in a generator. 43 Technetium generator  Technetium-99m (99mTc) is used in 90% of radionuclide imaging, as it fulfils most of the mentioned criteria.  With its gamma energy of 141 keV, it is easily collimated and easily absorbed in a fairly thin crystal, thus giving good spatial resolution.  With its short half-life (6 h) and pure gamma emission, a reasonably large activity can be administered, reducing noise in the image. 44 Technetium generator  Technetium-99m (99mTc) is supplied from a generator shielded with lead.  The generator contains an exchange column of alumina beads on which have been absorbed a compound of the parent 99Mo (which can be produced in a nuclear reactor and has a 67 h half-life). 45 Technetium generator Schematic of Technetium-99m generator 46 Technetium generator  When the generator is delivered, the activity of the daughter 99mTc has built up to its maximum, equal to that of the parent 99Mo.  The daughter is decaying as quickly as it is being formed by the decay of its parent.  The daughter and the parent decay together with the halflife of the parent (67 h). 47 Technetium generator Decay of activity of molybdenum-99 and growth and regrowth of activity of technetium-99m in a generator that is eluted daily. 48 Technetium generator  The technetium-99m is washed off the column (eluted) as sodium pertechnetate with sterile saline solution.  This flows under pressure from a reservoir through the column into a rubber-capped sterile container.  The precise design of the generator and pressure system depends on the manufacturer.  Elution takes a few minutes and leaves behind the molybdenum, which is firmly attached to the column. 49 Technetium generator  As you have seen in the previous figure, the 99mTc in the column increases with the same half-life of 6 h.  After 24 h, the activity has grown again to a new maximum (equilibrium) value.  Elution can be made daily, although it will be seen that the strength of successive eluents diminishes in line with the decay of 99Mo.  After a week, the generator is usually replaced and the old one is returned for recycling. 50 Uses of technetium-99m  Sodium pertechnetate- 99mTc is used for imaging the tissues:  the thyroid, the gastric mucosa (localisation of Meckel’s diverticulum) and the salivary glands.  Blocked from the thyroid by administration of potassium perchlorate, it can be used for cerebral blood flow and testicular imaging and mixed with bran porridge for gastricemptying studies. 51 next natur  99mTc can easily be labelled to a wide variety of usual Uses of technetium-99m compounds, for example : methylene diphosphonate (MDP): for bone imaging  hexamethyl propylene amine oxime (HMPAO): for cerebral imaging  dimercaptosuccinic acid (DMSA) and mercaptoacetyltriglycine (MAG3): for renal studies  iminodiacetic acid (HIDA): for biliary studies 52 Uses of technetium-99m  human serum albumin (HSA): imaging of liver, spleen and red bone marrow  diethylene triamine pentacetic acid (DTPA) aerosol (5µm particles): for lung ventilation studies  autologous red cells: for cardiac function  heat-damaged autologous red cells: for imaging the spleen  sestamibi or tetrofosmin: for cardiac perfusion imaging 53 other radionuclides and their uses  Iodine is trapped and metabolised by the thyroid, which was the first organ ever imaged, and 131I was the first radionuclide used for imaging.  131I was cheap, highly reactive and an excellent label.  131I is produced in a nuclear reactor and has a long half-life (8 days), but emits beta particles as well as energetic gamma rays (mainly 364 keV). 54 other radionuclides and their uses  131I has largely been replaced for imaging by 123I, which is more expensive, cyclotron produced, has a half-life of 13 h, and decays by electron capture emitting 159 keV gamma rays.  123I is also more expensive than, but otherwise superior to, 125I with its long half-life (60 days) and low photon energy (35 keV)  Note that both 131I and 125I are used for therapy: - 131I is used for thyroid ablation - 125I is used as brachytherapy seeds 55 other radionuclides and their uses  Xenon-133 (133Xe): is produced in a nuclear reactor, has a half-life of 5.2 days and emits beta particles and low energy gamma rays (81 keV)  It is an inert gas, although somewhat soluble in blood and fat, and is used, with rebreathing, in lung ventilation imaging. 56 other radionuclides and their uses  Krypton-81m (81mKr): another inert gas, is generatorproduced, has a half-life of 13 s and emits 190 keV gamma rays. The generator is eluted with compressed air, and the patient inhaling the air (i.e. 81mKr mixture) in pulmonary ventilation studies.  The parent, Rubidium-81 (81Rb), has a short half-life (4.7 h), which presents transport difficulties and means that it must be used the day it is delivered. 57 other radionuclides and their uses  Gallium-67 (67Ga): is cyclotron-produced, has a half-life of 67 h, and decays by electron capture, emitting gamma rays of three main energies (93, 184, 296 and 388 keV).  Gallium citrate is used to detect tumours and abscesses. 58 other radionuclides and their uses  Indium-111 (111In): is cyclotron-produced, has a half-life of 67 h, and decays by electron capture, emitting 171.3 keV and 245.4 keV gamma rays.  It is used to label white blood cells and platelets for locating abscesses and thrombosis. 59 other radionuclides and their uses Indium-113 (113mIn): is sometimes used instead of 111In, is generator-produced, has a half-life of 100 min, and emits only gamma rays, but they have a high energy (390 keV). 60 Positron emitters  Positron emitters are needed for PET (positron emission tomography) scans.  The most common PET radionuclide is 18F, with a half-life of 110 min.  18F often used in the form of 18F 2-fluroro-2deoxyglucose (2FDG) for brain and heart metabolism as well as eplipsy and tumour detection. 61 Positron emitters  Other radionuclides used for PET are carbon-11 (11C), nitrogen-13 (13N), oxygen-15 (15O) and rubidium-82 (82Rb), but these positron emitters have very short half-lives: 20 min, 10 min, 2 min and 75 s, respectively.  82Rb, which is produced from a strontium-82 generator that lasts about 1 month, can be used for myocardial prefusion imaging. 62 Positron emitters  Technetium-94m (94mTc), cyclotron-produced with a half-life of 50 min.  It can be used to label many pharmaceuticals already available for 99mTc imaging.  94mTc sestamibi can be used in tumour imaging studies utilising PET. 63 64 Nuclear Medicine Physics Module Dr Mohammed Saeed Alqahtani Lecture 3 Preparation of radiopharmaceuticals 2 Preparation of radiopharmaceuticals  The preparation usually involves the simple mixing or shaking at room temperature of the radionuclide (e.g. 99mTc as sodium pertechnetate) with the compound to be labelled (e.g. MDP) and other necessary chemicals.  Shielded syringes are used to transfer the components between sterile vails.  The manipulations are carried out under sterile conditions in a workstation; for example, a glove box or a sterile laminar down-flow cabinet. 3 Preparation of radiopharmaceuticals Laminar down-flow cabinet A glove box 4 Preparation of radiopharmaceuticals  All surfaces are impervious: continuous floors, gloss-painted walls, and formicatopped or stainless steel benches.  Normal sterile procedures must be followed, and entry is via an air lock and changing room.  With preparation time being necessarily short for PET radiopharmaceuticals, automated synthesis devices using microprocessor control are commonly used.  Using this technology reduce the radiation exposure of the staff 5 Preparation of radiopharmaceuticals Automated synthesis device for PET tracers’ production 6 Radiopharmaceuticals quality control  Quality control includes testing for: A) radionuclide purity:  For example, testing for contamination with 99Mo, which would give an unnecessary dose to the patient, by measuring any gamma radiation from 99Mo after blocking off the gamma rays from 99mTc with 6mm lead. 7 Radiopharmaceuticals quality control  Quality control includes testing for: B) radiochemical purity:  For example, testing for free pertechnetate in a labelled 99mTc compound using chromatography. C) chemical purity:  For example, the spot colour test for alumina, which may have come from the 99Mo column and would interfere with labelling. 8 Radiopharmaceuticals quality control  Quality control includes testing for D) response of the radionuclide calibrator:  For example, testing the detector against a standard radioactive source with a long half-life. 9 Dose calibrator 10 Planar imaging 11 Planer imaging process  The patient is given an appropriate radiopharmaceutical, usually by intravenous injection.  The function of the radiopharmaceutical is, ideally, to concentrate in the organ or tissues of interest.  The role of radionuclide is to signal the location of the radiopharmaceutical by the emission of gamma rays. 12 Planer imaging process  The radionuclide most commonly used, 99mTc, emits 141keV gamma rays. The emitted gamma photons are detected by a gamma camera, and an image of the radioactive distribution is produced on a monitor screen. As gamma rays cannot be focused, instead of a lens a multi-hole collimator is used to delineate the image from the patient. 13 Large field of view (LFOV) gamma cameras  Diversified hardware and connections are assembled together to form a medical gamma ray detection instrument, also known as the gamma camera.  Each component plays an integral role in the identification of gamma photons and producing proper medical gamma images.  These slides elaborate on the conventional gamma imaging system’s chief elements only and does not provide an explanation of every single component and their detailed functions. 14 LFOV gamma imaging system  The major components observed in each gamma camera include a light guide, photomultiplier tube array, radiation shielding, scintillation crystal, collimator, electronics for energy positioning and differentiation. Additionally, there would be a display device and a computer for processing and demonstrating images and data 15 LFOV gamma imaging system 16 LFOV Gamma Camera Scintillators  The process of converting gamma rays into optical light is performed using a scintillation crystal.  As a part of a gamma camera design, several characteristics are considered before choosing the appropriate crystal for gamma ray detection.  To attain enhanced imaging performance suitable for clinical use, the scintillator chosen must be inexpensive, have short decay duration, with high atomic number, and high density and light output. 17 LFOV Gamma Camera Scintillators  the following table lists properties of common scintillators used in conventional gamma cameras: Properties Na(Tl) CsI(Na) CsI(Tl) Density (g cm-3) 3.67 4.51 4.51 Decay time (µs) 0.23 0.63 1 Refraction Index Photon yield (keV) 1.85 38 1.84 39 1.8 45 – 52 Hygroscopic Yes Yes Slightly Effective atomic number (Zeff) 50 54 54 420 540 Peak emission wavelength (nm) 415 18 LFOV Gamma Camera Scintillators  Sodium iodide (NaI) scintillators are the most widely utilised for radiation detection in conventional gamma ray imaging systems.  However, it has been found that NaI crystals have unwanted characteristics of moisture absorption and fragility; therefore, they are required to be sealed in airtight containers.  To enhance the NaI crystals reaction to the incident gamma photons, they can be doped with thallium (Tl) atoms, which improves the scintillator’s response to the gamma photons. 19 LFOV Gamma Camera Scintillators  As a result of photoelectric or Compton scattering interactions of the incident photons with the scintillator’s material, an energetic electron is released and moves within the scintillator and interacts with other atoms to produce more excitations and ionisations.  The resultant electrons that are in an excited state subsequently return to their stable state through realising their energy in a form of optical photons. 20 LFOV Gamma Camera Scintillators  Crystal design is an integral factor influencing the scintillation process.  It has been shown that consistently high sensitivity levels are recorded while utilising thick crystals, as they can absorb most incident gamma photons; however, a reduction of spatial resolution is recognised.  Conversely, gamma photons can escape thinner crystals easily, which will degrade the sensitivity of the detector. 21 LFOV Gamma Camera Scintillators  For medical imaging purposes, the usual thicknesses for the manufactured scintillators of gamma cameras is in the range 6 to 12.5 mm, and these thicknesses match the detection of gamma photons in the 141 keV range (i.e. 99mTc isotope energy). 22 LFOV Gamma Camera Scintillators 23 Photomultiplier tube (PMT)  There are two steps in the procedure of gamma detection using gamma cameras.  The process commences with an interaction between the scintillation crystal and the incident gamma photons.  Following this, the energy of these photons is deposited in the crystal and converted to visible optical photons. The transmitted light propagates and is guided towards an array of PMTs. 24 Photomultiplier tube (PMT)  The PMT is a high-voltage, sensitive, optical detector, which can detect and convert optical photons into a measurable electrical signal.  The PMT works on the directly proportional relationship between the electric current and the number of detected optical photons.  the PMT is a vacuum tube with an entrance window, an anode, photocathode, dynodes (electron multiplier), and focusing electrodes. 25 Photomultiplier tube (PMT)  The NaI scintillator transmits optical photons at a peak wavelength of 415 nm and these optical photons are received by the photocathode, which liberates photoelectrons (i.e. low energy phenomena: photoelectric effect).  The photoelectrons, produced by the photocathode, are directed by a focusing electrode towards the first dynode.  The collision between the primary electrons and the first dynode surface liberates more electrons. Consequently, the same step repeats between a series of dynodes with further stages of electron amplification. 26 Photomultiplier tube (PMT)  This process does not end until the electrons reach the final dynode.  This cascade procedure works as all the electrons are collected at the PMT’s anode. 27 Photomultiplier tube (PMT) 28 Gamma ray collimation principles  The gamma image produced by a conventional gamma camera is formed on a pixelated grid. The number of detected gamma photons is recorded for each pixel within the camera’s field of view.  Therefore, the formation of a gamma image is actually a true mapping for the radioactive agents in the targeted region of interest (i.e. the spatial locations of the detected gamma photons). 29 Gamma ray collimation principles  To enhance the produced gamma image quality, scattered gamma photons should be minimised to reduce image noise.  Additionally, improving the ability of the gamma camera to maximise the detection of primary gamma photons would improve the gamma imaging outcome. 30 Gamma ray collimation principles  When the process of nuclear scanning takes place, there are several elements that influence the appropriate type of collimator for gamma ray detection. Such as FOV dimension, targeted areas’ dimensions, and the desired level of sensitivity and spatial resolution.  the gamma rays that are emitted from the examined region in the patient are mapped onto the scintillator and represent the targeted tissues’ respective locations in the image.  The main drawback of this approach is that only gamma photons passing through the collimator’s holes can be registered and utilised to produce a gamma image; the other gamma photons will be absorbed by the collimator’s material. Therefore, the sensitivity of the gamma camera is affected.  The following slides show routinely used gamma camera collimators in nuclear medicine clinics. 31 Gamma ray collimation principles 32 Parallel hole collimator  The most common collimators for gamma image formation are the parallel hole collimators.  This type of collimator consists of a high density material plate (e.g. lead is a commonly used material) with hexagonal structured holes arranged in a close-packed hexagonal array.  Using this preferred hole structure and arrangement would maximise the exposed area of the gamma camera detector.  However, these holes can be manufactured in other structures, such as triangular, square, or circular holes. 33 Parallel hole collimator  Generally, the thickness of parallel hole collimators manufactured for traditional gamma cameras ranges between 25 and 80 mm, and they contain 3×104 - 9×104 holes.  The structure of the parallel bore arrays is symmetrical, with identical holes, surrounded by lead septa. 34 Parallel hole collimator  The parallel hole collimator allows incident gamma photons to pass through at a perpendicular angle.  Parallel hole collimators provide a superior level of sensitivity compared to pinhole collimators.  However, generally collimators impose considerable limitations on the FOV of the gamma imaging systems because most of the off-axis gamma photons are absorbed by the collimator body. 35 Parallel hole collimator  In practice, the parallel hole collimator allows several incidence angles because the hole diameter is not infinitesimally small and the spatial resolution quality of the gamma camera degrades with larger dimensions of the collimator’s holes, as these will allow a wider range of acceptance angles.  Using different gamma emitters also plays a significant role in the selection of the appropriate parallel-hole collimator; the energy of the gamma photons is the key factor to determine the septal thickness.  This is because the scattered gamma photon penetration for the collimator body must be minimised using an appropriate septal thickness to avoid the projection of inaccurate data on the gamma image. 36 Non-parallel hole collimator  Parallel hole collimators differ from diverging and converging collimators based on the field of view despite their corresponding exit plane dimensions.  The converging collimator gives a smaller FOV (used to scan small targeted areas such as during brain or cardiac scanning procedures); whereas, the diverging collimator provides a larger FOV in comparison to the parallel-hole collimator.  Diverging-hole collimators are utilised to collect gamma photons from a large region of interest (i.e. larger than a camera’s crystal) 37 Non-parallel hole collimator  To satisfy the needs of nuclear medicine clinics with small organ imaging procedures, such as parathyroid and thyroid scanning, pinhole collimators are appropriate.  The pinhole collimator has a cone-shaped structure made from metals, such as tungsten, lead or platinum.  The aperture has a diameter range of 2 to 6 mm.  It further demonstrates its effectiveness in examining bone joints, paediatric scans, and skeletal extremities nuclear scanning. 38 Non-parallel hole collimator  The spatial resolution requirements are different (i.e. higher spatial resolution is required) for small animal gamma imaging systems as the small targeted structures require 1-2 mm pinhole diameter or even lower. 39 Non-parallel hole collimator  The spatial resolution requirements are different (i.e. higher spatial resolution is required) for small animal gamma imaging systems as the small targeted structures require 1-2 mm pinhole diameter or even lower. 40 Non-parallel hole collimator  The spatial resolution requirements are different (i.e. higher spatial resolution is required) for small animal gamma imaging systems as the small targeted structures require 1-2 mm pinhole diameter or even lower. 41 Types of collimator  Low-energy collimator has thin septa (0.3 mm) and can be used with gamma rays of up to 150 keV (e.g. with 99mTc).  A general purpose collimator might have 20000 holes each 2.5 mm diameter, a resolution (at 10 cm from the face) of 9 mm, and sensitivity 150 cps MBq-1. 42 Types of collimator  A high-resolution collimator would have more and smaller holes and lower sensitivity;  It can be used where high resolution is required and the amount of radioactivity and the imaging times needed are acceptable. 43 Types of collimator  A high-sensitivity collimator would have fewer and larger holes and poorer resolution.  It can be used in dynamic imaging where short exposure times are necessary and the poorer resolution must be accepted. 44 Types of collimator  Medium-energy collimators, for use up to 400 keV (e.g. with 111In, 67Ga and 131I), have thicker septa (1.4 mm) and consequently fewer holes and lower sensitivity. 45 Tomography with radionuclides  Conventional planar gamma imaging produces a twodimensional projection of a three-dimensional distribution of a radiopharmaceutical.  The images of organs are superimposed, depth information is lost and contrast is reduced.  These deficiencies are addressed in emission tomography. 46 Tomography with radionuclides  There are TWO methods of emission tomography: A) Single-photon emission computed tomography (SPECT) B) Positron emission tomography (PET) 47 Single-photon emission computed tomography (SPECT)  In its simple form, a gamma camera with a parallel hole collimator rotates slowly in a circular orbit around the patient lying on a narrow cantilever couch.  Every 6°, the camera halts for 20 – 30s and acquires a view of the patient. 60 views are taken from different directions, each, however, comprising fewer counts than in conventional static imaging. 48 Single-photon emission computed tomography (SPECT)  Some 3 million counts are acquired in an overall scanning time of around 30 mins.  Image acquisition time is halved or the sensitivity improved by using a dual- or triple-headed camera. 49 Single-photon emission computed tomography (SPECT)  The camera must move on a sufficiently large circular orbit to miss the patient’s shoulders.  An elliptical orbit is sometimes used to minimise the gap between the collimator and the patient and so improve the resolution.  Rotation of 180° is useful option (e.g. in cardiac tomography). 50 Single-photon emission computed tomography (SPECT)  Some dedicated equipment uses three or four gamma cameras equally spaced around the rotating gantry, thus improving sensitivity.  The increase sensitivity can be used for faster patient throughput or to improve the resolution. 51 Single-photon emission computed tomography (SPECT)  SPECT studies can be presented either as a series of slices or as a three-dimensional display.  The 3-D display is particularly effective when the image is rotated continuously on the computer screen, as persistence of vision helps to reduce the effect of image noise. 52 Single-photon emission computed tomography (SPECT)  Thallium studies of myocardial infarctions and ischaemia are major uses of SPECT, along with quantitative cerebral blood flow.  Other applications, such as the detection of tumours and bone irregularities, are increasing in clinical usefulness, particularly when SPECT is combined with CT. 53 Single-photon emission computed tomography (SPECT)  Gated acquisitions are also possible with SPECT as in planar imaging (e.g. MUGA studies).  Cardiac gated myocardial SPECT can be used to obtain quantitative information about myocardial perfusion, thickness of the myocardium, left ventricular ejection fraction, stroke volume and cardiac output.  Indeed, SPECT is probably the clinical standard for assessment of myocardial ischaemia, although PET mow offers more accuracy and better spatial resolution. 54 55