Single-photon emission computed

tomography

Introduction
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine
tomographic imaging technique using gamma rays.[1] It is very similar to conventional nuclear medicine
planar imaging using a gamma camera. Emission tomography as a medical imaging technique detects
the radiation emitted by radioisotopes injected into the body to provide measurements of regional
tissue function in vivo. In single-photon emission computed tomography (SPECT) photons emitted from
the radiotracer in the body are detected by the system as independent events. (art1) However, it is able
to provide true 3D information. This information is typically presented as cross-sectional slices through
the patient, but can be freely reformatted or manipulated as required.

The advantages of emission tomography include the ability to utilise tracers specifically targeting molecular
pathways in tissue in vivo.
The technique requires delivery of a gamma-emitting radioisotope (a radionuclide) into the patient,
normally through injection into the bloodstream. On occasion, the radioisotope is a simple soluble
dissolved ion, such as an isotope of gallium(III). Most of the time, though, a marker radioisotope is
attached to a specific ligand to create a radioligand, whose properties bind it to certain types of tissues.
This marriage allows the combination of ligand and radiopharmaceutical to be carried and bound to a
place of interest in the body, where the ligand concentration is seen by a gamma camera.

Clinical applications of SPECT are found in oncology, cardiology, neurology and

psychiatry. Over the last decade, SPECT has been increasingly combined with CT components to enhance the
functional information with structural/anatomical images. Although initially the combination of functional with
anatomical modalities was experimental the rapid development of hybrid imaging systems of SPECT/CT has
established both as diagnostic tools in current clinical practice.

Basic Principles of SPECT Imaging

Radioactive decay refers to the inherent process by which the nucleus of an unstable atom loses energy
by spontaneous emission of ionising radiation (photons, alpha particles, beta particles). This may be an
internal process of the nucleus of the unstable atom but may occasionally also involve an inner electron
of the radioactive atom (electron capture and internal conversion). Radionuclides or radioisotopes are
such unstable atoms exhibiting the property of radioactive decay and can be naturally occurring or
artificially produced. Technetium-99m (where ‘m’ refers to the metastable state of the isotope) is one of
the most frequently used radioisotopes in nuclear medicine and decays (half-life: 6.006 h) to
technetium-99 via the emission of gamma rays (photons) of 140 keV of energy. Technetium-99m ( 99mTc)
is usually produced by the longer-lived molybdenum-99 (half-life: 2.75 days) (Fig. 1) thus permitting on-
site availability of the isotope for medical use.

Fig. 1 Schematic diagram of the production of 99mTc from the parent 99Mo

The energy of 99mTc is within the ideal range for efficient detection with current technology and
together with the convenient half-life (long enough for handling the radiolabelling and imaging process,
short enough to limit unnecessary radiation dose to patients). On-site production from the longer-lived
parent radionuclide makes 99mTc an attractive choice for medical imaging. PET photons are detected in
coincidence and can thus be traced back to the same annihilation event, unlike in SPECT, where data
collection is based on the recording of photons detected independently from each other. Single-photon
detection relies on the use of physical collimation in order to obtain directional information for the
incident photons. Detection of photons is performed by a gamma camera comprising a single or multiple
detector heads. The active part of the detector head is usually a large scintillation crystal capable of
recording the incident photons that have not been absorbed by the material of the physical collimator
positioned in front of the crystal. A collimator is manufactured by suitable material (lead or tungsten) of
high probability of interaction with the photons and comprises a large number of holes to allow access
of incident photons only in the direction parallel to the holes. Photons reaching the collimator in other
directions have a very high probability of being absorbed by the material of the collimator. A typical size
of the collimator holes is 1.4–3.0 mm with bore length of 24–60 mm. The process of photons detection
is described in Fig. 2
Fig. 2 Schematic diagram of the photon detection process by the gamma camera leading to the formation of an image

As photons are emitted from areas of radiopharmaceutical uptake at various depths within the body,
these may undergo a number of interactions with the matter. As a result, there will be photons reaching
the gamma camera detector(s) either uninterrupted or after being deflected form their original direction
of emission. Those photons reaching the detector at directions parallel to the collimator holes will
interact with the crystal resulting in ionisation of the crystal. A suitable crystal material should have a
high probability of interaction with the incident photons. Typically, gamma cameras use sodium iodide
doped with thallium, NaI(Tl). As a scintillation crystal, NaI(Tl) has suitable properties (density, atomic
number) for a high efficiency in detecting photons at the energy range used in conventional nuclear
medicine, while other materials may be more suited for detection of photons at higher energies such as
the 511 keV annihilation photons in PET. De-excitation of the scintillation crystal occurs via emission of
light which can be detected by the photomultiplier tubes (PMTs) at the back of the crystal. PMTs are
devices that can convert the scintillation light into a pulse of electrical current (Fig. 3).

Fig. 3 Schematic diagram of a photomultiplier tube

Scintillation light from the crystal is converted into electrons at the photocathode of the PMT. These
electrons will be accelerated by the electric potential between the metallic anodes of the PMT
successively producing more elections at each anode thus finally amplifying the initial signal to an
electric pulse detectable by the electronics of the gamma camera. Processing of the pulse by the
electronics of the system will determine the energy and position of the incident event and thus its
acceptance within the predefined energy window and, after analogue to digital conversion (ADC), the
coordinates of the event within the image matrix. Photons may undergo a number of interactions with
the matter. The predominant type of interaction with the matter at the energies of photons used in
emission tomography is the Compton effect(Fig 4).

Fig. 4 Compton scattering

As a beam of photons passes through tissue as a result of interactions with the electrons of the atoms, a
number of photons will be deflected from their initial direction. This may cause some photons to be
directed away from the detector, while others may reach the detector with an incident direction
different to that of their original emission. The first scenario (photon deflected away from original
direction of detection) describes photon attenuation, while the second scenario (photon deflected
towards the detector with altered direction) describes photon scattering. The impact of photon
attenuation is generally an underestimation of the activity concentration which becomes more severe
towards the centre of the object. The result of photon scatter is an added background-like effect
typically leading to an overestimation of activity concentration in lowuptake areas. A number of
methods have been employed in order to perform attenuation and scatter correction (refer to section
below). In single-photon emission tomography (SPECT), a series of planar projections acquired with the
gamma camera at various angles around the patient (Fig. 12.4) is used to derive transverse images of
the activity distribution within the body.
Fig. 5 Schematic diagram of data acquisition in SPECT

Each planar image acquired at a particular angle of the camera rotation, called a projection, contains
information at each pixel of the integral of counts across the body. A series of projection data over the
full rotation of the camera around the subject is usually required in order to calculate cross-sectional
images of the activity distribution within the body. This is done by use of image reconstruction
algorithms which fall into two broad categories: Analytical methods (filtered back-projection, FBP)
directly project the acquired sum of counts onto the image matrix at the direction of acquisition of the
particular projection resulting, after all acquired projections have been superimposed, to the formation
of an image representing the cross-sectional activity distribution. Statistical methods, such as the
maximum likelihood expectation maximisation (MLEM) (Shepp and Vardi 1982) or its accelerated
version, ordered subsets expectation maximisation (OSEM) (Hudson and Larkin 1994), rely on an
iterative process where an estimation of the image representing the activity distribution is successively
improved until the statistical comparison of the projections calculated from this estimate and the
projections measured with the gamma camera finally reaches some set criteria of agreement. Statistical
(or iterative) image reconstruction methods tend to be subject to non-uniform rate of convergence
across different areas of the image and are substantially more demanding in terms of computational
processing capacity compared to FBP. On the other hand, statistical methods tend to offer advantages in
terms of signal-to-noise and the ability to incorporate details about the detection process thus allowing
accurate photon attenuation correction and scatter correction.

Application
SPECT can be used to complement any gamma imaging study, where a true 3D representation can
be helpful, e.g., tumor imaging, infection (leukocyte) imaging, thyroid imaging or bone scintigraphy.
Because SPECT permits accurate localisation in 3D space, it can be used to provide information
about localised function in internal organs, such as functional cardiac or brain imaging.
The most common uses of SPECT are to help diagnose or monitor brain disorders,
heart problems and bone disorders.

Brain disorders (Functional brain imaging)

Usually, the gamma-emitting tracer used in functional brain imaging is 99mTc-HMPAO

(hexamethylpropylene amine oxime). 99mTc is a metastable nuclear isomer that emits gamma rays that
can be detected by a gamma camera. Attaching it to HMPAO allows 99mTc to be taken up by brain tissue
in a manner proportional to brain blood flow, in turn allowing cerebral blood flow to be assessed with
the nuclear gamma camera.

SPECT can be helpful in determining which parts of the brain are being affected by:

 Dementia

 Clogged blood vessels

 Seizures

 Epilepsy

 Head injuries

Because blood flow in the brain is tightly coupled to local brain metabolism and energy use, the 99mTc-
HMPAO tracer (as well as the similar 99mTc-EC tracer) is used to assess brain metabolism regionally, in an
attempt to diagnose and differentiate the different causal pathologies of dementia. Meta-analysis of
many reported studies suggests that SPECT with this tracer is about 74% sensitive at diagnosing
Alzheimer's disease vs. 81% sensitivity for clinical exam (cognitive testing, etc.). More recent studies
have shown the accuracy of SPECT in Alzheimer's diagnosis may be as high as 88%. In meta analysis,
SPECT was superior to clinical exam and clinical criteria (91% vs. 70%) in being able to differentiate
Alzheimer's disease from vascular dementias.This latter ability relates to SPECT's imaging of local
metabolism of the brain, in which the patchy loss of cortical metabolism seen in multiple strokes differs
clearly from the more even or "smooth" loss of non-occipital cortical brain function typical of
Alzheimer's disease. Another recent review article showed that multi-headed SPECT cameras with
quantitative analysis result in an overall sensitivity of 84-89% and an overall specificity of 83-89% in
cross sectional studies and sensitivity of 82-96% and specificity of 83-89% for longitudinal studies of
dementia.
99m
Tc-HMPAO SPECT scanning competes with fludeoxyglucose (FDG) PET scanning of the brain, which
works to assess regional brain glucose metabolism, to provide very similar information about local brain
damage from many processes. SPECT is more widely available, because the radioisotope used is longer-
lasting and far less expensive in SPECT, and the gamma scanning equipment is less expensive as well.
While 99mTc is extracted from relatively simple technetium-99m generators, which are delivered to
hospitals and scanning centers weekly to supply fresh radioisotope, FDG PET relies on FDG, which is
made in an expensive medical cyclotron and "hot-lab" (automated chemistry lab for
radiopharmaceutical manufacture), and then delivered immediately to scanning sites because of the
natural short 110-minute half-life of Fluorine-18.

Heart problems (Myocardial perfusion imaging)

Myocardial perfusion imaging (MPI) is a form of functional cardiac imaging, used for the diagnosis of
ischemic heart disease. The underlying principle is that under conditions of stress, diseased myocardium
receives less blood flow than normal myocardium. MPI is one of several types of cardiac stress test.

A cardiac specific radiopharmaceutical is administered, e.g., 99mTc-tetrofosmin (Myoview, GE

healthcare), 99mTc-sestamibi (Cardiolite, Bristol-Myers Squibb). Following this, the heart rate is raised to
induce myocardial stress, either by exercise or pharmacologically with adenosine, dobutamine, or
dipyridamole (aminophylline can be used to reverse the effects of dipyridamole).

SPECT imaging performed after stress reveals the distribution of the radiopharmaceutical, and therefore
the relative blood flow to the different regions of the myocardium. Diagnosis is made by comparing
stress images to a further set of images obtained at rest. As the radionuclide redistributes slowly, it is
not usually possible to perform both sets of images on the same day, hence a second attendance is
required 1–7 days later (although, with a Tl-201 myocardial perfusion study with dipyridamole, rest
images can be acquired as little as two hours post-stress). However, if stress imaging is normal, it is
unnecessary to perform rest imaging, as it too will be normal; thus, stress imaging is normally performed
first.

MPI has been demonstrated to have an overall accuracy of about 83% (sensitivity: 85%; specificity:
72%), and is comparable with (or better than) other non-invasive tests for ischemic heart disease.

Because the radioactive tracer highlights areas of blood flow, SPECT can check for:

 Clogged coronary arteries. If the arteries that feed the heart muscle become narrowed
or clogged, the portions of the heart muscle served by these arteries can become
damaged or even die.

 Reduced pumping efficiency. SPECT can show how completely your heart chambers
empty during contractions.
Bone disorders
Areas of bone healing or cancer progression usually light up on SPECT scans, so this
type of test is being used more frequently to help diagnose hidden bone fractures.
SPECT scans can also diagnose and track the progression of cancer that has spread to
the bones.

Study Radiois Emissio Half- Radiopharmaceutical Activit Rotation Projections Image Time per
otope n energy life y (degrees) resolution projection (s)
(keV) (MBq)
Bone scan technetium- 140 6 Phosphonates / 800 360 120 128 x 128 30
99m hours Bisphosphonates
Myocardial technetium- 140 6 tetrofosmin; Sestamib 700 180 60 64 x 64 25
perfusion scan 99m hours i
Sestamibi technetium- 140 6 Sestamibi
parathyroid scan 99m hours
Brain scan technetium- 140 6 HMPAO; ECD 555- 360 64 128 x 128 30
99m hours 1110
Neuroendocrine iodine- 159 13 MIBG 400 360 60 64 x 64 30
or neurological 123 or iodine hours
tumor scan -131 or 8
days
White cell scan indium- 171 & 67 in vitro labelled 18 360 60 64 x 64 30
111 & 245 hours leucocytes
technetium-
99m

Image reconstruction
Reconstructed images typically have resolutions of 64×64 or 128×128 pixels, with the pixel sizes ranging
from 3–6 mm. The number of projections acquired is chosen to be approximately equal to the width of
the resulting images. In general, the resulting reconstructed images will be of lower resolution, have
increased noise than planar images, and be susceptible to artifacts.

Scanning is time consuming, and it is essential that there is no patient movement during the scan time.
Movement can cause significant degradation of the reconstructed images, although movement
compensation reconstruction techniques can help with this. A highly uneven distribution of
radiopharmaceutical also has the potential to cause artifacts. A very intense area of activity (e.g., the
bladder) can cause extensive streaking of the images and obscure neighboring areas of activity. This is a
limitation of the filtered back projection reconstruction algorithm. Iterative reconstruction is an
alternative algorithm that is growing in importance, as it is less sensitive to artifacts and can also correct
for attenuation and depth dependent blurring.
Attenuation of the gamma rays within the patient can lead to significant underestimation of activity in
deep tissues, compared to superficial tissues. Approximate correction is possible, based on relative
position of the activity. However, optimal correction is obtained with measured attenuation values.
Modern SPECT equipment is available with an integrated X-ray CT scanner. As X-ray CT images are an
attenuation map of the tissues, this data can be incorporated into the SPECT reconstruction to correct
for attenuation. It also provides a precisely registered CT image, which can provide additional
anatomical information.

Scatter of the gamma rays as well as the random nature of gamma rays can also lead to the degradation
of quality of SPECT images and cause loss of resolution. Scatter correction and resolution recovery are
also applied to improve resolution of SPECT images.[7]