lecture notes 11 - nuclear diagnostic imaging

Nuclear Diagnostic Imaging

Basic Principles

In the diagnostic imaging two kinds of modalities can be differentiated. On one side the anatomical imaging, providing a very accurate visualization of the internal structures of the human body; and the functional imaging, which is aimed to quantify the physiological processes taking place inside the human body without influencing them. One of the most widely spread practices used for this purpose are contained in the Nuclear Medicine Diagnostics.

Terminology

Radionuclide –

An atom with an unstable nucleus,

The radionuclide undergoes radioactive decay, and emits a gamma ray(s) and/or subatomic particles.

These particles constitute ionizing radiation.

Radionuclides may occur naturally, but can also be artificially produced.

Radionuclides are also referred to as radioactive isotopes or radioisotopes.

Radiopharmaceuticals

Radioactive pharmaceuticals use tracers in the diagnosis and treatment of many diseases.

Many radiopharmaceuticals use technetium (Tc-99m).

Over 30 different radiopharmaceuticals based on Tc-99m are used for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood and tumors.

Isotopes –

different forms of an element each having different atomic mass (mass number).

Isotopes of an element have nuclei with the same number of protons (the same atomic number) but different numbers of neutrons.

Isotopes have different mass numbers, which give the total number of nucleons— the number of protons plus neutrons.

Isotopes and nuclides are used interchangeably

nearly identical chemical behavior but with different atomic masses and physical properties.

Every chemical element has one or more isotopes.

Stable and Unstable Isotopes

Isotopes utilized in nuclear medicine fall into two broad categories: Stable and Unstable. Stable isotopes do not undergo radioactive decay.

A "stable isotope" is any of two or more forms of an element whos nuclei contains the same number of protons and electrons, but a different number of neutrons. Stable isotopes remain unchanged indefinitely,

"unstable" (radioactive) isotopes undergo spontaneous disintegration.


Stable isotopes

Used for diagnosis of disease, to understand metabolic pathways in humans, and to answer fundamental questions in nature.

help to better understand a process, trace a compound from a particular source, measure the concentration of a chemical in a sample, or measure the rate of a related process.

used in nuclear medicine: include carbon-13, nitrogen-15 and oxygen-18 as well as noble gas isotopes.

Diagnostic Radiopharmaceuticals

Some chemicals are absorbed by specific organs.

Thyroid takes up iodine

Brain consumes quantities of glucose

Radioisotopes can be attached to biologically active substances.

Diagnostic radiopharmaceuticals can be used to examine

blood flow to the brain

functioning of the liver, lungs, heart or kidneys

assess bone growth

predict the effects of surgery

The amount of the radiopharmaceutical given to a patient is just sufficient to obtain the required information before its decay.

The radiation dose received is medically insignificant.

The patient experiences no discomfort during the test and after a short time there is no trace that the test was ever done.

The non-invasive nature of this technology, together with the ability to observe an organ functioning from outside the body, makes this technique a powerful diagnostic tool.

The ideal radioisotope used for diagnosis emits gamma rays of sufficient energy to escape from the body and has a half-life short enough for it to decay away shortly after imaging is completed.

The main principle of the Nuclear Medical Diagnostics is the non invasive determination of physiological processes. Different pharmaceuticals specific to the targeted physiological process are available. A radiopharmaceutical is used in tracer quantities with no pharmacological effect. This tracer is distributed, metabolized, and excreted according to their chemical structure. The biological functions can be displayed as images, numerical data or time-activity curves.

Radionuclide production

The above mentioned radiopharmaceuticals are compounds of biomedical interest which have attached radionuclides as labels that allow us to quantify specific physiological processes. The radionuclides are made by bombarding nuclei of stable atoms with sub- nuclear particles so as to cause nuclear reactions that convert a stable nucleus into an unstable one. The different ways to produce radionuclides can be of primary source like the Reactor-production and the Accelerator-production or secondary source like the Radionuclide Generators.

For many years the nuclear reactors have been the largest source of radionuclides but nowadays inside the Nuclear Medicine Facilities it is easier to find a kind of accelerator called cyclotron and/or radionuclide generators which will be briefly described later on. A commonly used accelerator for the production of nuclear medicine radionuclides is the cyclotron. Which consists of a pair of hollow; semicircular metal electrodes (called “dees” because of their shape), positioned between the poles of a large electromagnet. The dees are separated from one another by a narrow gap. Its principle of operation is the use of the magnetic force on a

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moving charge to bend moving charges into a semicircular path between accelerations by an applied electric field. The applied electric field accelerates electrons between the "dees" of the magnetic field region. The field is reversed at the cyclotron frequency to accelerate the electrons back across the gap.

Radionuclide generators consist of a parent-daughter radionuclide pair contained in an apparatus that permits separation and extraction of the daughter from the parent in a physiological solution.

Technetium 99m

Tc 99m is the most commonly used radionuclide (80%)

Tc is the chemical symbol of technetium. 99 is its mass number. The m denotes 'metastable', which means it has a stable nucleus (unlike most radioactive material) – but has extra energy which it gives up as gamma rays.

It is useful for several reasons:

It can be easily combined with several pharmaceuticals.

It gives off gamma rays at 140MeV which is a good match to the sensitivity range of the Gamma Camera.

Its half-life of six hours is long enough to allow practical imaging but not so long that the patient, public and environment are over-burdened with radiation.

It is a pure gamma emitter.

Decays by a process called "isomeric transition“

emits gamma rays and low energy electrons,

but no high energy beta particles so the radiation dose to the patient is low.

Generated from molybdenum-99

Mo-99 has a half-life of 66 hours

progressively decays to technetium-99 Technetium 99m Generators

Generators are supplied to hospitals from the nuclear reactor where the isotopes are made.

Tc-99m Generator

The desirable characteristics of a generator are that it should be easily transportable; that the separation of daughter from parent should happen easily, sterile and pyrogen-free with a high yield of separation, no radionuclide impurities, the parent should have a reasonable half life;

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the daughter should present an ideal half life and gamma energy and something very important that the chemistry of the daughter allows hospital preparation.

It consists of a lead pot enclosing a glass tube containing the radioisotope molybdenum-99, with a half-life of 66 hours, which progressively decays to technetium-99.

Tc-99 is washed out of the lead pot by saline solution when it is required.

After two weeks or less the generator is returned for recharging.

Nuclear Decay Modes

In order to reach a stable state the radionuclides decay in different modes, namely emission,

ß-emission,

positron (ß+) emission,

isomeric transition ( emission),

internal conversion (IC),

electron capture (EC)

nuclear fission.

For diagnostic nuclear medicine purposes the and nuclear fission are of relatively little importance. The other modes are briefly described.

The isomeric transition consists in the emission of -rays. An alternative to -ray emission that is especially common among metastable states is decay by internal conversion. In this process, the nucleus decays by transferring energy to an orbital electron which is ejected instead of the -ray. It is as if the -ray were “internally absorbed” by collision with an orbital electron.

In radioactive decay by positron emission (ß+), a proton in the nucleus is transformed into a neutron and a positron that is the antiparticle of an ordinary electron. The positron combines with the negative electron in an annihilation reaction. There is a “back to back” emission of annihilation photons that is required for conservation of momentum for the stationary electron-positron pair. The mass-energy equivalent of each particle is 0.511 MeV. Positron emitters are useful in nuclear medicine because two photons are generated per nuclear decay event. The precise directional relationship between the annihilation photons permits the use of “coincidence counting” techniques.

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Figure - 2


The electron capture decay is also known as “inverse ß-decay”. In this decay an orbital electron is captured by the nucleus and combines with a proton to form a neutron.

Positron emission and EC have the same effect on the parent nucleus. Both are isobaric decay modes that decrease atomic number by one.

Among the radioactive nuclides, one finds that ß+ decay occurs more frequently among lighter elements, whereas EC is more frequently among heavier elements, since in heavy elements orbital electrons tend to be closer to the nucleus and are more easily captured. For example 18F decays 3% of the cases by EC and 97% by ß+ emission.

The range of coverage of particle emission in tissue is shown in the following table:

Particle Energy Coverage

(very local Therapy) few MeV < 1mm

ß (Therapy) 100 KeV – 1MeV ~ few mm

(Imaging) 100 – 500 KeV > few cm

The type and energy of emissions from the radionuclide determine the availability of useful photons for counting or imaging. For external detection of a radionuclide inside the body it is very important to consider the interactions that they have with the different materials.

The three main interactions of high-energy photons through matter are the

1. photoelectric effect,

2. Compton scattering

3. pair production.

The following graphic shows the probability of interaction versus photon energy for absorbers

of different atomic numbers. From it we can observe that the intensity of photons reaching a detector decreases as the mass attenuation coefficient increases for the same absorber thickness and photon energy. The mass attenuation coefficient tends to increase with increasing atomic number at the same photon energy, so materials with high atomic numbers (and, hence, high mass attenuation coefficients) are normally chosen to shield x and gamma radiation.

Detector systems for nuclear medicine

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Figure - 3


The photons encountered in nuclear medicine most often have substantially higher energies than those used in x-ray imaging. Film-based imaging systems such as those found in dentistry clinics don’t work at these high energies, because the high-energy photons just pass straight through the film.

The detector of choice for nuclear medicine is the scintillation detector. This consists of a crystal attached to a photomultiplier tube (see figure 4).

The crystal is a scintillator: when a gamma ray interacts with it, a flash of visible light is produced.

Optically coupled to the scintillator is a photomultiplier tube (PMT), which turns incoming light into an electrical pulse.

A scintillation detector on its own is not an imaging device. We can use it to detect the presence of a high-energy photon. We can use it to measure its energy as well, within certain limits.

Photomultiplier tube

The small amount of light from the scintillation crystals has to be somehow increased in order to be measured. The photomultiplier tubes (PMT) are devices that do this task and allow a more accurate measurement of this light. The principle of operation of these devices is that when incident light reaches the entrance window, which is coated with a photo emissive substance called photocathode; electrons are ejected and focused towards a metal plate called dynode. The dynode is maintained at a positive voltage relative to the photocathode attracting the electrons to it. The dynodes are coated with a material having relatively high secondary emission characteristics. A high speed photoelectron striking the first dynode surface ejects several secondary electrons from it. Which are attracted to the next dynode which is maintained at 50-150 V higher potential than the first one here the electrons are again ejected to the next dynode and so on. At each dynode the electrons get multiplied.

The conversion efficiency for visible light to electrons is called the Quantum Efficiency of PMTs.

The main requirements for light detectors are a high quantum efficiency to transfer as many of the photons as possible into charge carriers to ensure high signal amplitude; a fast read out (for timing applications like PET) and a good amplitude resolution because that can be translated into high energy resolution.

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Figure 4. A scintillation detector. The incoming gamma ray interacts with the scintillator to produce a scintillation flash. Photons from the scintillation flash dislodge photoelectrons from the photocathode in the photomultiplier tube. These are accelerated to the nearest dynode, where they dislodge further electrons. This process continues down the tube, resulting in a cascade of electrons. There are usually about ten dynodes, and a multiplication factor of about 6 at each dynode. The efficiency of the photocathode is such that about 3–5 photoelectrons are released for every ten incident scintillation photons. The intensity rise time and decay time of the scintillation flash are determined by the scintillator—the total charge collected from the back of the photomultiplier tube is a measure of the energy deposited by the gamma ray.


However, to obtain an image, we need the position of the interaction of the photon with the detector, and we need the direction of the photon’s flight. These last two pieces of information can be obtained using a gamma camera (also known as an Anger Camera, after its inventor, Hal Anger).

Gamma Camera

The major components of a gamma camera

1. A large area scintillation crystal (6-12.5 mm thick x 25 to 50 cm in diameter)

2. A collimator: used to define the direction of the detected . rays. Consisting of a lead plate, that contains a large number of holes.

The collimator ensures that only those photons with paths parallel to the collimator holes strike the detector (figure 6).

3. A light guide (highly reflecting material like TiO2 and an optical glass window)

4. An array of photomultiplier tubes; ( Figure-5) coupled optically to the back face of the crystal and arranged in a hexagonal pattern. Typical PM tube sizes are 5 cm diameter. A typical gamma camera has between 30 and 100 PM tubes. Which are encased in a thin magnetic shield to prevent changes in the gain due to changes in the orientation of the gamma camera relatively to the Earth’s magnetic field.

5. Positioning and summing circuits (preamplifiers, pulse-height analyzers, automatic gain control, pulse pile-up rejection circuits, etc.)

6. Computer

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Figure 5 - The detector consists of a crystal of thallium-doped sodium iodide of area approximately 50 × 60 cm and about 1–2 cm thick. This crystal is viewed by about 50 PMTs. Since sodium iodide is hygroscopic, the crystal must be enclosed in an airtight seal.

Figure 6. A gamma camera collimator. The collimator prevents photons which are not approximately perpendicular to the collimator holes from interacting with the detector. The field of view for the detector element behind each collimator hole is divergent, so that in a gamma camera spatial resolution degrades as the distance to the object is increased. The collimators are usually made of lead. For medium energy photon imaging, the holes are typically about 3 mm across, with the sides (the ‘septa’) being about 1 mm thick and the collimator depth about 40–50 mm. Not all collimators use parallel holes—there are converging or diverging slant-hole collimators,and pin-hole collimators which can be used for very high resolution imaging.


Planar imaging

The simplest way to use an Anger camera is analogous to a plain x-ray film. The camera is placed adjacent to the patient and both patient and camera are kept still while the signal accumulates. This results in a single planar view of the patient

The Gamma photons from the patient(who has been injected with a radioactive pharmaceutical) strike the NaI crystal. The crystal scintillates in response to incident gamma radiation. After the flash of light is produced, it is detected. Photomultiplier tubes (PMTs) behind the crystal detect the fluorescent flashes (events) and a computer sums the counts. The computer reconstructs and displays a two dimensional image of the relative spatial count density on a monitor. This reconstructed image reflects the distribution and relative concentration of radioactive tracer elements present in the organs and tissues imaged.

The advantage of this method is that it is fast and computationally simple, but the disadvantage is that structures that overlay each other along the line of sight to the camera are difficult to distinguish. In addition, gamma rays arising from tracer concentrations on the far side of the patient tend to be scattered and absorbed (‘attenuated’) by the patient’s body, rendering them difficult to see. It may therefore be necessary to acquire more than one view of the patient (from different angles) to obtain the necessary information.

Positron emission tomography (PET)

An exciting and developing area of nuclear medicine is the field of positron emission tomography or PET.

In PET, the radionuclide used for labelling is a positron emitter rather than a gamma emitter. The positrons are emitted with an energy of the order of 1 MeV, and being beta particles, they have a very short range in human tissue (»1–2 mm).

When an emitted positron has given up most of its kinetic energy through collisions with ambient particles (i.e., it has reached thermal energy) it combines with an electron and rapidly undergoes an annihilation reaction, in which the all the energy of the electron and positron pair is converted into radiation.

The most likely course of this reaction is the production of two photons, each of energy very close to 511 keV (equivalent to the rest mass of the electron). In order to conserve momentum, the two photons are emitted in exactly opposite directions.

PET imaging is best performed using a dedicated system with specialized high-energy detectors and operating on the principle of coincidence detection.

Coincidence detection takes advantage of the fact that each annihilation event gives rise to two photons travelling in opposite directions to obtain information about the direction of flight of the photons without the use of a collimator.

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Figure 7. A gamma camera

Figure 8: PET - Coincidence detection


Dedicated PET systems usually consist of a series of rings of detector units sharing common electronics (see figure 9). In coincidence detection, the time of arrival of each detected photon interaction is checked to see if it is contemporaneous with a photon seen at any other detector. If so, the two photons are deemed to be in coincidence, and are assumed to have come from the same annihilation event. This event can then be assigned to a line of response joining the two detectors (figure 10).

During a PET scan, the lines of response are populated with data according to the number of coincidence events recorded. The data in the lines of response can then be reordered into views and reconstructed into three-dimensional images.

PET/CT principles

The PET images offer a great functional contrast but don’t provide too good anatomical resolution. On the other hand, the CT images provide a very good anatomical representation but it is difficult to find out functional information out of it. The combination of PET and CT in a single device provides simultaneous structural and biochemical information (fused images) under almost identical conditions, minimizing the temporal and spatial differences between the two imaging modalities.

Among the advantages that having this two modalities together offers we can find that the patient stays on the same table for both acquisitions minimizing any intrinsic spatial misalignment; the total examination of PET is notably reduced; because of the transmission

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Figure 9 : A dedicated PET system

Figure 10. The concept of coincidence detection. If pulses from separate detector elements overlap in time, it is assumed that the detectors registered photons arising from the same annihilation event. In practice, events areassigned digital time stamps, which are compared to find coincidences.


scan is being done by the CT reducing in this way the costs of maintenance and of replacing the radioactive source available in the standard PET scanners.

The PET/CT examination starts with the injection of the radionuclide. After an uptake time the patient is positioned as comfortable as possible on the table of the PET/CT scanner.

Normally a CT-topogram follows. Then the table moves into the start position of the PET system and the emission scan is initiated. By the time the emission PET scan is completed the CT transmission images have been already reconstructed and available for the attenuation and scatter corrections of the emission data. The total time for the images to be ready for diagnostics is restricted to the reconstruction time which is more or less the time taken to have enough counts for each bed position of the PET acquisition.

Single Photon Emission Tomography (SPECT)

A SPECT (Single Photon Emission Computed Tomopraphy) camera consists of a gamma camera or a set of gamma cameras mounted on a gantry so that the detector can record projections from many equally spaced angular intervals around the body.

SPECT images are captured from the uniform emission of single photons—bursts of energy—emitted by the decay of radioisotopes.

The advantage of the SPECT technique is that the full three-dimensional nature of the tracer distribution in the patient can be appreciated, but the disadvantage is that it takes longer and requires more signal to reduce noise in the crosssectional images.

In practice, both SPECT and planar imaging methods are frequently used in concert. Attenuation of signal is still a problem in SPECT, but since views are taken from all around the patient, it is the centre of the tracer distribution that is affected most.

Attenuation correction schemes for SPECT are becoming more widely available, and very substantial efforts have been made in recent years to optimize the treatment of the noisy data during the image reconstruction process.

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lecture notes 11 - nuclear diagnostic imaging

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