Positron emission tomography - computed tomography

(PET-CT or PET/CT)

• PET-CT or PET/CT is a medical imaging technique using a device which combines in a

single gantry system both a Positron Emission Tomography (PET) and an x-ray Computed
Tomography, so that images acquired from both devices can be taken sequentially, in the
same session from the patient and combined into a single superposed (co-registered) image.
• PET/CT combines two scan techniques in one exam - a PET scan and a CT scan.
• PET and CT are both standard imaging tools.
• PET gives functional imaging and CT gives anatomic imaging. Thus, PET-CT adds precision
of anatomic localization to functional imaging, which was previously lacking from pure PET
imaging.
• The functional imaging obtained by PET, which depicts the spatial distribution of metabolic
or biochemical activity in the body can be more precisely aligned or correlated with
anatomic imaging obtained by CT scanning.
• A CT scan takes pictures from all around the body and uses a computer to put them
together. A PET scan uses a very small amount of an injected radioactive drug to show
where cells are active in the body.
• A PET scan can measure such vital functions as blood flow, oxygen use, and glucose
metabolism, which helps doctors identify abnormal from normal functioning organs and
tissues. The scan can also be used to evaluate the effectiveness of a patient’s treatment plan,
allowing the course of care to be adjusted if necessary.
• CT sees a 360-degree view of the body, useful for taking 3D pictures. Similar to traditional
X-rays, CT scans show a higher level of detail and take more accurate pictures of the brain
and body.
• PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans,
with the combination (called "co-registration") giving both anatomic and metabolic
information (i.e., what the structure is, and what it is doing biochemically).
• Because the two scans can be performed in immediate sequence during the same session,
with the patient not changing position between the two types of scans, the two sets of
images are more-precisely registered, so that areas of abnormality on the PET imaging can
be more perfectly correlated with anatomy on the CT images. This is very useful in showing
detailed views of moving organs or structures with higher anatomical variation, which is
more common outside the brain.
• The information from the PET and CT scans are very different but complementary to each
other. The PET scan shows areas with increased metabolic activity, while the CT scan shows
detailed anatomical locations. A combination of these two images together enables a doctor
to tell whether a region with high metabolic activity is significant, and if so, to state

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definitively where that location is. Often the PET/CT is repeated to monitor the effect of
treatment of a particular disease.

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 PET:
• Certain isotopes produce positrons that react with electrons to emit two photons at 511 keV
in opposite directions.
• PET takes advantage of this property to determine the source of the radiation.
• If one path is shorter, then the opposite path is longer and the average signal level is the
same without regard to patient attenuation or point of origin.
• These isotopes have two means of decay, which result in the annihilation of an electron.
• In one case, the nucleus can capture an orbital electron that combines with positive change,
alternatively, the nucleus can emit the positive charge as a positron that travels a short
distance to combine with an external electron.
• The combination of the negative and positive particles annihilates the charges and masses of
each, energy and momentum are conserved, and two 511 keV gamma-rays are emitted in
opposite directions.
• Positrons emitted by the nucleus have kinetic energy, so they travel few mm before the
annihilation emission event.
• The travel distance and interaction blur the dimensions of the region of origin when it is
detected.
• The broadening effect is the width of the pulse measured at 10% level.
• The dimensions of a useful picture element would be about twice these values because of
other spreading effects, such as system bandwidth optical effects.
• The property of simultaneous emission of two gamma rays in opposite directions gives PET
the ability to locate the region of origin.
• The advantages of PET over conventional nuclear imaging include the clarity of cross-
sectional views and the availability of positron emitters that can be compounded as
metabolites. It is possible to map metabolic activity in the brain by using tagged compounds
to observe uptake and clearance.
• The measures quantity in PET imaging is the concentration, in tissue, of the positron
emitter.

About the scanner and scanning procedure:

• A PET scanner is a large machine with a round, doughnut shaped hole in the middle,
similar to a CT or MRI unit.
• Within this machine are multiple rings of detectors that record the emission of energy from
the radiotracer in the body.
• The CT scanner is typically a large, box-like machine with a hole, or short tunnel, in the
center.
• Patient will lie on a narrow examination table that slides into and out of this tunnel.
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• Rotating around the patient, the x-ray tube and electronic x-ray detectors are located
opposite each other in a ring, called a gantry.
• The computer workstation that processes the imaging information is located in a separate
control room, where the technologist operates the scanner and monitors the examination in
direct visual contact and usually with the ability to hear and talk to patient with the use of a
speaker and microphone.
• Combined PET/CT scanners are combinations of both scanners and look similar to both the
PET and CT scanners.
• A computer aids in creating the images from the data obtained by the camera or scanner.
• A PET-CT scan takes CT pictures of the structures of the body.
• At the same time, a mildly radioactive drug shows up areas of the body where the cells are
more active than normal (in case of cancer).
• The scanner combines both of these types of information.
• This allows doctor to see any changes in the activity of cells and know exactly where the
changes are happening.
• A small tube (cannula) is put into one of the veins in the back of hand or arm.
• Then radioactive drug (tracer) as an injection is given through the tube.
• One has to wait for at least one hour afterwards for the body to absorb the radioactive drug.
• Scanning is done for 30 and 90 minutes, depending on which parts of the body are scanned.
• The amount of radiation given for scanning is small, the same as when one is having an X-
ray.

Advantages:
• It has special benefits of both PET and CT in one procedure.
• The combination of PET to visualize the biological processes of life and the anatomical
imaging capabilities of CT provides the finest resolution.
• PET and CT combination provides high-quality images with both speed and accuracy.
• It is a highly sensitive imaging technique.

Images:

Diagnostics

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 A complete body PET / CT Fusion
image

A - CT image; B - PET image; C - Coregistered PET and CT images.

The bright red/yellow masses show hypermetabolic areas of the pelvis with metastases of a
previous, surgically removed colon carcinoma in a 69-yrs old woman

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 Specific example: Fluorodeoxyglucose (FDG) imaging:

• Most commonly PET utilizes 18F-FDG as a radiotracer, the short half-life of which (110 min)
reduces radiation exposure compared with other commonly used radionuclides such as
99mTechnetium (6 hours) and 201Thallium (72 hours).
• The radiation exposure from 18F results in internal exposure to the patient and low level
external exposure to other people in their vicinity.
• The most commonly used radioisotope in PET F-18, is not produced in any nuclear reactor,
but rather in a circular accelerator called a cyclotron. The cyclotron is used to accelerate
protons to bombard the stable heavy isotope of oxygen O-18. The O-18 constitutes about
0.20% of ordinary oxygen (mostly O-16), from which it is extracted. The F-18 is then
typically used to make FDG.
• An example of how PET-CT works in the work-up of FDG metabolic mapping follows:
 Before the exam, the patient fasts for greater than 4-hours;
 In the day of the exam, the patient rests lying for a minimum of 15 min, in order to quiet
down muscular activity, which might be interpreted as abnormal metabolism;
 An intravenous bolus injection of a dose of recently produced 2-FDG or 3-FDG is made,
usually by a vein in one of the arms. Dosage ranges from 0.1 to 0.2 mCi per kg of body
weight;
 After one or two hours, the patient is placed into the PET-CT device, usually lying in a
supine position with his/her arms resting at the sides, or brought together above the
head, depending on the main region of interest (ROI);
 An automatic bed moves head first into the gantry, first obtaining a topogram, also
called a scout view or surview, which is a kind of whole body flat sagittal section,
obtained with the X-ray tube fixed into the upper position;
 The operator uses the PET-CT computer console to identify the patient and examination,
delimit the caudal and rostral limits of the body scan onto the scout view, selects the
scanning parameters and starts the image acquisition period, which follows without
human intervention;
 The patient is automatically moved head first into the CT gantry, and the x-ray
tomogram is acquired;
 Now the patient is automatically moved through the PET gantry, which is mounted in
parallel with the CT gantry, and the PET slices are acquired;
 The patient may now leave the device, and the PET-CT software starts reconstructing
and aligning the PET and CT images.
• A whole body scan, which usually is made from mid-thighs to the top of the head, takes
from 5 minutes to 40 minutes depending on the acquisition protocol and technology of the
equipment used.

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• FDG imaging protocols acquires slices with a thickness of 2 to 3 mm.
• Hypermetabolic lesions are shown as false color-coded pixels or voxels onto the gray-value
coded CT images.
• Standardized Uptake Values are calculated by the software for each hypermetabolic region
detected in the image.
• It provides a quantification of size of the lesion, since functional imaging does not provide a
precise anatomical estimate of its extent.
• The CT can be used for that, when the lesion is also visualized in its images (this is not
always the case when hypermetabolic lesions are not accompanied by anatomical changes).
• FDG doses in quantities sufficient to carry out 4-5 examinations are delivered daily, twice or
more times per day, by the provider to the diagnostic imaging center.
• For uses in stereotactic radiation therapy of cancer, special fiducial marks are placed in the
patient's body before acquiring the PET-CT images.
• The slices thus acquired may be transferred digitally to a linear accelerator which is used to
perform precise bombardment of the target areas using high energy photons (radiosurgery).
• How does CT work?:
 CT stands for Computerized Tomography (commonly known as a CAT scan).
 During the CT scan, the scanner emits X-rays, which go through the patient to detectors.
 The computer uses this information to generate cross-sectional images of anatomical
structures.
 The body will not come in contact with the scanner itself.
 One will be lying on a narrow table, which will move through the scanner or detectors.
 Each cross-sectional picture or slice gives detailed anatomic location and changes in the
anatomy.
 The use of oral and IV contrast agents can enhance the details by highlighting the
gastrointestinal tract (filled by oral contrast) and other organs and blood vessels (filled
with IV contrast).
• How does PET work?:
 PET stands for Positron Emission Tomography.
 PET scans measure metabolic activity and molecular function by using a radioactive
glucose injection.
 The radiotracer (specific e.g., F-18 FDG) is injected into the patient.
 The PET scanner detects the radiation emitted from the patient, and the computer
generates three-dimensional images of tissue function or cell activity in the tissues of the
body.

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  These functional images can detect disease earlier than the anatomic information gained
from CT alone.
 Like the CT scanner, the body will never come in contact with scanner itself. There are
no side effects from this injection and procedure.
 All cells use glucose as an energy source.
 However, cancer cells grow faster than normal healthy cells and they use glucose at
much higher rate than normal cells.
 This is the basis of imaging with F-18 FDG for cancer detection in PET scan.
• How do PET/CT radiation doses compare with doses from other examinations?:
 A PET/CT test has two components: a PET scan and a CT, which are done together.
 The radiation exposure from CT has a very wide range depending on the type of the
test, the area of the body scanned and the purpose of the test.
 In its simplest form, a CT scan is used only for the localization of abnormalities seen on a
PET scan (non-diagnostic scan).
 The radiation dose from such a scan can be low (e.g. an effective dose of about 7 mSv for
a whole body study).
 However, the effective dose from a high resolution diagnostic scan can be quite high (up
to 30 mSv for a whole body CT scan).
 The effective dose from a PET scan is modest and depends on the activity of the injected
FDG (18F-Fluoro deoxyglucose) and is typically 8 mSv for adults using 400 MBq and is
the same whether a part of the body or the whole body is imaged.
 Major reductions in radiation doses from PET/CT scans can be achieved by modifying
the acquisition parameters for CT.
 Conventional radiographic examinations such as chest, abdominal and bone X rays also
give a radiation dose but only a fraction of that resulting from a CT examination.
 Examinations such as ultrasonography and magnetic resonance (MR) imaging do not
involve exposure to ionizing radiation.
• Just like glucose, FDG is actively transported into cells mediated by a group of structurally
related glucose transport proteins.
• Once intracellular, glucose (and therefore also FDG) are phosphorylated by hexokinase as
the first step in the glycolytic metabolism pathway.
• Normally, after being phosphorylated glucose continues along the glycolytic pathway for
energy production.
• FDG, on the other hand, cannot enter the glycolytic pathway and becomes effectively
trapped intracellularly as FDG-6-phosphate.
• Tumor cells display increased numbers of glucose transporters as well as higher levels of
hexokinase.

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• Most tumor cells are highly metabolically active with high mitotic rates that favor the more
inefficient anaerobic metabolic pathway which adds to the already increased glucose
demands.
• These combined mechanisms allow tumor cells to take up and retain higher levels of FDG
when compared to normal tissues.
• PET provides imaging of the whole body distribution of FDG, thus highlighting the
markedly increased metabolic activity of tumor cells.
• Sites of tumor involvement not obvious from cross-sectional images alone are often found,
such as lymph nodes involved by tumor which are not pathologically enlarged by size
criteria.
• An important concept regarding PET imaging is that FDG is not cancer specific and will
accumulate in any areas of high rates of metabolism and glycolysis.
• Therefore, increased uptake can be expected in all sites of hyperactivity at the time of FDG
administration (e.g. muscles and nervous system tissues); at sites of active inflammation or
infection (e.g. sarcoidosis, arthritis, pneumonia, etc.); and at sites of active tissue repair (e.g.,
surgical or traumatic wounds, healing fractures, etc.).

How is a PET scan different from a CT or MRI scan?:

One of the main differences between PET scans and other imaging tests like CT scan or MRI is
that the PET scan reveals the cellular level metabolic changes occurring in an organ or tissue.
This is important and unique because disease processes often begin with functional changes at
the cellular level.
A PET scan can often detect these very early changes whereas a CT or MRI detect changes a
little later as the disease begins to cause changes in the structure of organs or tissues.

Applications:
• PET and PET/CT scans are performed to:
 detect cancer.
 determine whether a cancer has spread in the body.
 assess the effectiveness of a treatment plan, such as cancer therapy.
 determine if a cancer has returned after treatment.
 determine blood flow to the heart muscle.
 determine the effects of a heart attack, or myocardial infarction, on areas of the heart.
 identify areas of the heart muscle that would benefit from a procedure such as
angioplasty or coronary artery bypass surgery (in combination with a myocardial
perfusion scan).

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  evaluate brain abnormalities, such as tumors, memory disorders, seizures and other
central nervous system disorders.
 map normal human brain and heart function.
• It is a highly sensitive imaging technique used in oncology, cardiology, neurology and in
infectious and inflammatory diseases.
• Currently, PET scans are most commonly used to detect cancer, heart problems (such as
coronary artery disease and damage to the heart following a heart attack), brain disorders
(including brain tumors, memory disorders, seizures) and other central nervous system
disorders.
• This is very useful in showing detailed views of moving organs or structures with higher
anatomical variation, which is more common outside the brain.
• In cancer: PET/CT is mainly used for diagnosis, staging or restaging malignant disease and
metastases and evaluation of treatment response. PET and CT allow physicians to pinpoint
the location of cancer within the body before making treatment recommendations. The
highly sensitive PET scan detects the metabolic signal of actively growing cancer cells in the
body and the CT scan provides a detailed picture of the internal anatomy that reveals the
location, size and shape of abnormal cancerous growths. Alone, each imaging test has
particular benefits and limitations but when the results of PET and CT scans are "fused"
together, the combined image provides complete information on cancer location and
metabolism. The two procedures, PET and CT, together provide information about the
location, nature of and the extent of the lesion. In other words, it answers questions like:
Where is the tumor, how big is it, is it malignant, benign or due to inflammatory change,
and has the cancer spread? PET-CT scans are used for many types of cancer and are
generally thought to be more accurate in diagnosing cancer than PET scans alone. From the
research, we know that in some cancers PET-CT scans can help to:
 Diagnose cancer
 Stage a cancer
 Make decisions about whether one can have surgery to remove cancer
 Make decisions about which is the best treatment for cancer
 Show how well the treatment is working
 Show the difference between scar tissue and active cancer tissue
 Check whether the cancer has come back
 Find the place in the body where the cancer first started to grow (primary cancer)
 After one has had treatment for cancer, a scan may show that there are still some signs
of the cancer left. But this may not be active cancer. It could be scar tissue left over from
cancer killed off by the treatment.
 A PET-CT scan can sometimes show whether this tissue is active cancer or not.

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  The level of detail of PET-CT images: (i) Helps oncologists reduce the amount of healthy
tissue that is treated; (ii) Frequently identifies previously unsuspected cancer-bearing
tissues; (iii) Allows for more effective and tailored treatments.
• It may also be used to differentiate dementia verses Alzheimer’s disease.

Limitations of PET/CT:
• Nuclear medicine procedures can be time consuming.
• It can take hours to days for the radiotracer to accumulate in the part of the body under
study and imaging may take up to several hours to perform, though in some cases, newer
equipment is available that can substantially shorten the procedure time.
• The resolution of structures of the body with nuclear medicine may not be as high as with
other imaging techniques, such as CT or MRI.
• However, nuclear medicine scans are more sensitive than other techniques for a variety of
indications, and the functional information gained from nuclear medicine exams is often
unobtainable by other imaging techniques.
• Test results of diabetic patients or patients who have eaten within a few hours prior to the
examination can be adversely affected because of altered blood sugar or blood insulin levels.
• Because the radioactive substance decays quickly and is effective for only a short period of
time, it is important for the patient to be on time for the appointment and to receive the
radioactive material at the scheduled time.
• Thus, late arrival for an appointment may require rescheduling the procedure for another
day.
• A person who is very obese may not fit into the opening of a conventional PET/CT unit.
• Combined/hybrid device is considerably more expensive.
• The other obstacle to a wider dissemination of PET-CT is the difficulty and cost of
producing and transporting the radiopharmaceuticals used for PET imaging, which are
usually extremely short-lived (for instance, the half-life of radioactive fluorine18 used to
trace glucose metabolism (using fluorodeoxyglucose, FDG) is two hours only.
• Its production requires a very expensive cyclotron as well as a production line for the
radiopharmaceuticals.

What are the benefits vs. risks of nuclear medicine?:

• Benefits
 Nuclear medicine examinations offer information that is unique—including details on
both function and structure—and often unattainable using other imaging procedures.
 For many diseases, nuclear medicine scans yield the most useful information needed to
make a diagnosis or to determine appropriate treatment, if any.
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  Nuclear medicine is less expensive and may yield more precise information than
exploratory surgery.
 By identifying changes in the body at the cellular level, PET imaging may detect the
early onset of disease before it is evident on other imaging tests such as CT or MRI.
• The benefits of a combined PET/CT scanner include:
 Greater detail with a higher level of accuracy; because both scans are performed at one
time without the patient having to change positions, there is less room for error.
 Greater convenience for the patient who undergoes two exams (CT & PET) at one
sitting, rather than at two different times.
• Risks
 Because the doses of radiotracer administered are small, diagnostic nuclear medicine
procedures result in relatively low radiation exposure to the patient, acceptable for
diagnostic exams.
 Thus, the radiation risk is very low compared with the potential benefits.
 Nuclear medicine diagnostic procedures have been used for more than five decades, and
there are no known long-term adverse effects from such low-dose exposure.
 The risks of the treatment are always weighed against the potential benefits for nuclear
medicine therapeutic procedures.
 Patient will be informed of all significant risks prior to the treatment and have an
opportunity to ask questions.
 Allergic reactions to radiopharmaceuticals may occur but are extremely rare and are
usually mild.
 Nevertheless, patient should inform the nuclear medicine personnel of any allergies
he/she may have or other problems that may have occurred during a previous nuclear
medicine exam.
 Injection of the radiotracer may cause slight pain and redness which should rapidly
resolve.
 Women should always inform their physician or radiology technologist if there is any
possibility that they are pregnant or if they are breastfeeding.

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