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.
Nuclear Diagnostic Imaging

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

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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
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

Figure 1: Cyclotron operation principle

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

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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;
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.

Figure - 2

Nuclear Decay Modes

• In order to reach a stable state the radionuclides decay in different modes, namely
α emission,
• ß-emission,
• positron (ß+) emission,
• isomeric transition (γ emission),
• internal conversion (IC),
• electron capture (EC)
• nuclear fission.

For diagnostic nuclear medicine purposes the α and nuclear fission are of relatively little
importance. The other modes are briefly described.
The isomeric transition consists in the emission of γ -rays. An alternative to γ -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 γ -ray. It is as if the γ -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

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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.
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

α (very local few MeV < 1mm

Therapy)
ß (Therapy) 100 KeV – 1MeV ~ few mm

γ (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

Figure - 3

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

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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
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.

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.
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

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(for timing applications like PET) and a good amplitude resolution because that can be
translated into high energy resolution.
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 Figure 5 - The detector consists of a crystal
holes strike the detector (figure 6). of thallium-doped sodium iodide of area
approximately 50 × 60 cm and about 1–2 cm
3. A light guide (highly reflecting material thick. This crystal is viewed by about 50
like TiO2 and an optical glass window) 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.
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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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 Figure 7. A gamma
(PMTs) behind the crystal detect the fluorescent flashes (events) camera
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.

Figure 8: PET - Coincidence detection

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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.
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.

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 are
assigned digital time stamps, which are compared to find
coincidences.
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.

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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
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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