Positron emission tomography - AbsoluteAstronomy.com

Positron emission tomography (PET) is nuclear medicine

Nuclear medicine

In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...

imaging

Medical imaging

Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...

technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma ray

Gamma ray

Gamma radiation, also known as gamma rays or hyphenated as gamma-rays and denoted as γ, is electromagnetic radiation of high frequency . Gamma rays are usually naturally produced on Earth by decay of high energy states in atomic nuclei...

s emitted indirectly by a positron

Positron

The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. The positron has an electric charge of +1e, a spin of ½, and has the same mass as an electron...

-emitting radionuclide

Radionuclide

A radionuclide is an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide, in this process, undergoes radioactive decay, and emits gamma...

(tracer), which is introduced into the body on a biologically active molecule. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. In modern scanners, three dimensional imaging is often accomplished with the aid of a CT X-ray scan

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

performed on the patient during the same session, in the same machine.

If the biologically active molecule chosen for PET is FDG, an analogue of glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, the concentrations of tracer imaged then give tissue metabolic activity, in terms of regional glucose uptake. Although use of this tracer results in the most common type of PET scan, other tracer molecules are used in PET to image the tissue concentration of many other types of molecules of interest.

History

The concept of emission and transmission tomography was introduced by David E. Kuhl

David E. Kuhl

David Edmund Kuhl isan American scientist specializing in nuclear medicine.He is well known for his pioneering work in positron emission tomography. Dr...

, Luke Chapman and Roy Edwards in the late 1950s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania

University of Pennsylvania

The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...

. Tomographic imaging techniques were further developed by Michel Ter-Pogossian, Michael E. Phelps

Michael E. Phelps

Michael Edward Phelps is a professor and an American biophysicist. He is known for being one of the fathers of positron emission tomography . Phelps was born in 1939 in Cleveland, Ohio. He spent his early life as a boxer, winning the coveted Golden Gloves...

and others at the Washington University School of Medicine

Washington University School of Medicine

Washington University School of Medicine , located in St. Louis, Missouri, is one of the graduate schools of Washington University in St. Louis. One of the top medical schools in the United States, it is currently ranked 4th for research according to U.S. News and World Report and has been listed...

.

Work by Gordon Brownell, Charles Burnham and their associates at the Massachusetts General Hospital

Massachusetts General Hospital

Massachusetts General Hospital is a teaching hospital and biomedical research facility in the West End neighborhood of Boston, Massachusetts...

beginning in the 1950s contributed significantly to the development of PET technology and included the first demonstration of annihilation radiation for medical imaging. Their innovations, including the use of light pipes, and volumetric analysis have been important in the deployment of PET imaging. In 1961, James Robertson and his associates at Brookhaven National Laboratory built the first single-plane PET scan, nicknamed the "head-shrinker."

One of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In particular, the development of labeled 2-fluorodeoxy-D-glucose (2FDG) by the Brookhaven group under the direction of Al Wolf and Joanna Fowler was a major factor in expanding the scope of PET imaging. The compound was first administered to two normal human volunteers by Abass Alavi

Abass Alavi

Abass Alavi is Professor of Radiology and Neurology. He is currently the Director of Research Education in the Division of Nuclear Medicine at the University of Pennsylvania....

in August 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ. Later, the substance was used in dedicated positron tomographic scanners, to yield the modern procedure.

The logical extension of positron instrumentation was a design using two 2-dimensional arrays. PC-I was the first instrument using this concept and was designed in 1968, completed in 1969 and reported in 1972. The first applications of PC-I in tomographic mode as distinguished from the computed tomographic mode were reported in 1970. It soon became clear to many of those involved in PET development that a circular or cylindrical array of detectors was the logical next step in PET instrumentation. Although many investigators took this approach, James Robertson and Z.H. Cho were the first to propose a ring system that has become the prototype of the current shape of PET.

The PET/CT scanner, attributed to Dr David Townsend and Dr Nutt was named by TIME Magazine as the medical invention of the year in 2000.

Description

Operation

To conduct the scan, a short-lived radioactive tracer isotope

Isotope

Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...

is injected into the living subject (usually into blood

Blood

Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

circulation). The tracer is chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest; then the subject is placed in the imaging scanner. The molecule most commonly used for this purpose is fluorodeoxyglucose

Fluorodeoxyglucose

Fludeoxyglucose or fluorodeoxyglucose , commonly abbreviated 18F-FDG or FDG, is a radiopharmaceutical used in the medical imaging modality positron emission tomography...

(FDG), a sugar, for which the waiting period is typically an hour. During the scan a record of tissue concentration is made as the tracer decays.

As the radioisotope undergoes positron emission

Positron emission

Positron emission or beta plus decay is a type of beta decay in which a proton is converted, via the weak force, to a neutron, releasing a positron and a neutrino....

decay (also known as positive beta decay

Beta decay

In nuclear physics, beta decay is a type of radioactive decay in which a beta particle is emitted from an atom. There are two types of beta decay: beta minus and beta plus. In the case of beta decay that produces an electron emission, it is referred to as beta minus , while in the case of a...

), it emits a positron, an antiparticle of the electron

Electron

The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...

with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on the isotope), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron. The encounter annihilates both electron and positron, producing a pair of annihilation

Electron-positron annihilation

Electron–positron annihilation occurs when an electron and a positron collide. The result of the collision is the annihilation of the electron and positron, and the creation of gamma ray photons or, at higher energies, other particles:...

(gamma

Gamma ray

) photon

Photon

In physics, a photon is an elementary particle, the quantum of the electromagnetic interaction and the basic unit of light and all other forms of electromagnetic radiation. It is also the force carrier for the electromagnetic force...

s moving in approximately opposite directions. These are detected when they reach a scintillator

Scintillator

A scintillator is a special material, which exhibits scintillation—the property of luminescence when excited by ionizing radiation. Luminescent materials, when struck by an incoming particle, absorb its energy and scintillate, i.e., reemit the absorbed energy in the form of light...

in the scanning device, creating a burst of light which is detected by photomultiplier

Photomultiplier

Photomultiplier tubes , members of the class of vacuum tubes, and more specifically phototubes, are extremely sensitive detectors of light in the ultraviolet, visible, and near-infrared ranges of the electromagnetic spectrum...

tubes or silicon avalanche photodiode

Avalanche photodiode

An avalanche photodiode is a highly sensitive semiconductor electronic device that exploits the photoelectric effect to convert light to electricity. APDs can be thought of as photodetectors that provide a built-in first stage of gain through avalanche multiplication. From a functional standpoint,...

s (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite direction (it would be exactly opposite in their center of mass frame, but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal "pairs" (i.e. within a timing-window of a few nanoseconds) are ignored.

Localization of the positron annihilation event

The most significant fraction of electron-positron decays result in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence, it is possible to localize their source along a straight line of coincidence (also called the line of response, or LOR). In practice, the LOR has a finite width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500 picoseconds rather than about 10 nanoseconds, it is possible to localize the event to a segment of a chord

Chord (geometry)

A chord of a circle is a geometric line segment whose endpoints both lie on the circumference of the circle.A secant or a secant line is the line extension of a chord. More generally, a chord is a line segment joining two points on any curve, such as but not limited to an ellipse...

, whose length is determined by the detector timing resolution. As the timing resolution improves, the signal-to-noise ratio

Signal-to-noise ratio

Signal-to-noise ratio is a measure used in science and engineering that compares the level of a desired signal to the level of background noise. It is defined as the ratio of signal power to the noise power. A ratio higher than 1:1 indicates more signal than noise...

(SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems.

Image reconstruction using coincidence statistics

A technique much like the reconstruction of computed tomography

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

(CT) and single-photon emission computed tomography (SPECT) data is more commonly used, although the data set

Data set

A data set is a collection of data, usually presented in tabular form. Each column represents a particular variable. Each row corresponds to a given member of the data set in question. Its values for each of the variables, such as height and weight of an object or values of random numbers. Each...

collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see Image reconstruction of PET).

Using statistics collected from tens-of-thousands of coincidence events, a set of simultaneous equations for the total activity of each parcel of tissue along many LORs can be solved by a number of techniques, and, thus, a map of radioactivities as a function of location for parcels or bits of tissue (also called voxel

Voxel

A voxel is a volume element, representing a value on a regular grid in three dimensional space. This is analogous to a pixel, which represents 2D image data in a bitmap...

s), may be constructed and plotted. The resulting map shows the tissues in which the molecular tracer has become concentrated, and can be interpreted by a nuclear medicine physician

Nuclear Medicine Physician

Nuclear Medicine Physicians are medical specialists that use tracers, usually radiopharmaceuticals, for diagnosis and therapy. Nuclear medicine procedures are the major clinical applications of molecular imaging and molecular therapy...

or radiologist in the context of the patient's diagnosis and treatment plan.

Combination of PET with CT or MRI

PET scans are increasingly read alongside CT or magnetic resonance imaging

Magnetic resonance imaging

Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

(MRI) scans, the combination ("co-registration"

Image registration

Image registration is the process of transforming different sets of data into one coordinate system. Data may be multiple photographs, data from different sensors, from different times, or from different viewpoints. It is used in computer vision, medical imaging, military automatic target...

) giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners. 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

Image registration

, 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.

At the Jülich Institute of Neurosciences and Biophysics, the world's largest PET/MRI device began operation in April 2009: a 9.4-tesla

Tesla (unit)

The tesla is the SI derived unit of magnetic field B . One tesla is equal to one weber per square meter, and it was defined in 1960 in honour of the inventor, physicist, and electrical engineer Nikola Tesla...

magnetic resonance tomograph (MRT) combined with a positron emission tomograph (PET). Presently, only the head and brain can be imaged at these high magnetic field strengths.

Radionuclides

Radionuclide

s used in PET scanning are typically isotope

Isotope

s with short half-lives

Half-life

Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

such as carbon-11 (~20 min), nitrogen-13

Nitrogen-13

Nitrogen-13 is a radioisotope of nitrogen used in positron emission tomography . It has a half life of a little under ten minutes, so it must be made at the PET site...

(~10 min), oxygen-15 (~2 min), and fluorine-18

Fluorine-18

Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....

(~110 min). These radionuclides are incorporated either into compounds normally used by the body such as glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

(or glucose analogues), water

Water

Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

, or ammonia

Ammonia

Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

, or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as radiotracers. It is important to recognize that PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radiolabeled with a PET isotope. Thus, the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are continuing to be synthesized; as of this writing there are already dozens in clinical use and hundreds applied in research. At present, however, by far the most commonly used radiotracer in clinical PET scanning is Fludeoxyglucose, an analogue of glucose that is labeled with fluorine-18.

Due to the short half-lives of most radioisotopes, the radiotracers have traditionally been produced using a cyclotron

Cyclotron

In technology, a cyclotron is a type of particle accelerator. In physics, the cyclotron frequency or gyrofrequency is the frequency of a charged particle moving perpendicularly to the direction of a uniform magnetic field, i.e. a magnetic field of constant magnitude and direction...

in close proximity to the PET imaging facility. The half-life of fluorine-18 is long enough that radiotracers labeled with fluorine-18 can be manufactured commercially at offsite locations and shipped to imaging centers. Recently rubidium

Rubidium

Rubidium is a chemical element with the symbol Rb and atomic number 37. Rubidium is a soft, silvery-white metallic element of the alkali metal group. Its atomic mass is 85.4678. Elemental rubidium is highly reactive, with properties similar to those of other elements in group 1, such as very rapid...

-82 generators have become commercially available. These contain strontium-82 which decays by electron capture

Electron capture

Electron capture is a process in which a proton-rich nuclide absorbs an inner atomic electron and simultaneously emits a neutrino...

to positron emitting rubidium-82.

11C-Metomidate is used to detect tumors of adrenocortical origin.

Limitations

The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy, where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.

Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers that can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with fluorine-18, which has a half-life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82, which can be created in a portable generator and is used for myocardial perfusion

Perfusion

In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...

studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and hot labs have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines

Because the half-life of fluorine-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.

Image reconstruction

The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection (typically, within a window of 6 to 12 nanoseconds of each other) of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred. Modern systems with a higher time resolution (roughly 3 nanoseconds) also use a technique (called "Time-of-flight") where they more precisely decide the difference in time between the detection of the two photons and can thus localize the point of origin of the annihilation event between the two detectors to within 10 cm.

Coincidence events can be grouped into projection images, called sinogram

Sinogram

Sinogram can mean,* a Chinese character even when used in a different language, such as Japanese , Korean or Vietnamese* a tetragram which follows the graphic conventions of Chinese characters, e.g...

s. The sinograms are sorted by the angle of each view and tilt (for 3D images). The sinogram images are analogous to the projections captured by computed tomography

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

(CT) scanners, and can be reconstructed in a similar way. However, the statistics of the data are much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. As such, PET data suffer from scatter and random events much more dramatically than CT data does.

In practice, considerable pre-processing of the data is required - correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time

Dead time

For detection systems that record discrete events, such as particle and nuclear detectors, the dead time is the time after each event during which the system is not able to record another event....

correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).

Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. However, shot noise

Shot noise

Shot noise is a type of electronic noise that may be dominant when the finite number of particles that carry energy is sufficiently small so that uncertainties due to the Poisson distribution, which describes the occurrence of independent random events, are of significance...

in the raw data is prominent in the reconstructed images and areas of high tracer uptake tend to form streaks across the image. Also, FBP treats the data deterministically - it does not account for the inherent randomness associated with PET data, thus requiring all the pre-reconstruction corrections described above.

Iterative expectation-maximization algorithm

Expectation-maximization algorithm

In statistics, an expectation–maximization algorithm is an iterative method for finding maximum likelihood or maximum a posteriori estimates of parameters in statistical models, where the model depends on unobserved latent variables...

s are now the preferred method of reconstruction. These algorithms compute an estimate of the likely distribution of annihilation events that led to the measured data, based on statistical principles. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements.

Attenuation correction: As different LORs must traverse different thicknesses of tissue, the photon

Photon

s are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray

X-ray

X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...

CT equipment, however earlier equipment offered a crude form of CT using a gamma ray

Gamma ray

(positron

Positron

The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. The positron has an electric charge of +1e, a spin of ½, and has the same mass as an electron...

emitting) source and the PET detectors.

While attenuation-corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.

2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.

There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).

3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources. The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction.

Applications

PET is both a medical and research tool. It is used heavily in clinical oncology

Oncology

Oncology is a branch of medicine that deals with cancer...

(medical imaging

Radiology

Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...

of tumor

Tumor

A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

s and the search for metastases

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray

X-ray

computed tomography

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

(CT), magnetic resonance imaging

Magnetic resonance imaging

Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

(MRI) and functional magnetic resonance imaging

Functional magnetic resonance imaging

Functional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used to measure the hemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of neuroimaging...

(fMRI), ultrasound

Ultrasound

Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

and single-photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET and SPECT are capable of detecting areas of molecular biology

Molecular biology

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

detail (even prior to anatomic change). PET scanning does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera

Gamma camera

A gamma camera, also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy...

fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower. However, for institutions with low demand for PET, this may allow on-site imaging, instead of referring patients to another center, or relying on a visit by a mobile scanner.

PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

Oncology

Oncology is a branch of medicine that deals with cancer...

: PET scanning with the tracer fluorine-18

Fluorine-18

Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....

(F-18) fluorodeoxyglucose

Fluorodeoxyglucose

Fludeoxyglucose or fluorodeoxyglucose , commonly abbreviated 18F-FDG or FDG, is a radiopharmaceutical used in the medical imaging modality positron emission tomography...

(FDG), called FDG-PET, is widely used in clinical oncology

Oncology

Oncology is a branch of medicine that deals with cancer...

. This tracer is a glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

analog

Analog (chemistry)

In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...

that is taken up by glucose-using cells and phosphorylated by hexokinase

Hexokinase

A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

(whose mitochondrial form is greatly elevated in rapidly growing malignant

Malignant

Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

tumours). A typical dose of FDG used in an oncological scan is 200-400 MBq

Becquerel

The becquerel is the SI-derived unit of radioactivity. One Bq is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. The Bq unit is therefore equivalent to an inverse second, s−1...

for an adult human. Because the oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

atom that is replaced by F-18 to generate FDG is required for the next step in glucose metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

added by hexokinase

Hexokinase

. This means that FDG is trapped in any cell that takes it up, until it decays, since phosphorylated

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma

Hodgkin's lymphoma

Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...

, non-Hodgkin lymphoma

Non-Hodgkin lymphoma

The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....

, and lung cancer

Lung cancer

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis—a fact that becomes especially useful in searching for tumor metastasis

Metastasis

, or for recurrence after a known highly active primary tumor is removed. Because individual PET scans are more expensive than "conventional" imaging with computed tomography

Computed tomography

X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

(CT) and magnetic resonance imaging

Magnetic resonance imaging

Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

(MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment

Health technology assessment

Health Technology Assessment is a multi-disciplinary field of policy analysis that examines the medical, economic, social and ethical implications of the incremental value, diffusion and use of a medical technology in health care....

; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice.

Neuroimaging

Neurology
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...

: PET neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is, in general, believed to be correlated, and has been measured using the tracer oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

-15. However, because of its 2-minute half-life, O-15 must be piped directly from a medical cyclotron
Cyclotron
In technology, a cyclotron is a type of particle accelerator. In physics, the cyclotron frequency or gyrofrequency is the frequency of a charged particle moving perpendicularly to the direction of a uniform magnetic field, i.e. a magnetic field of constant magnitude and direction...

for such uses, which is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability. PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....

s) have been developed for PET that are ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

for specific neuroreceptor subtypes such as [¹¹C] raclopride
Raclopride
Raclopride is a synthetic compound that acts as an antagonist on D2 dopamine receptors.It can be radiolabelled with the carbon-11 radioisotope and used in positron emission tomography scanning to assess the degree of dopamine binding to the D2 Dopamine receptor.For example, one study found...

and [¹⁸F] fallypride for dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

D2/D3 receptors, [¹¹C]McN 5652 and [¹¹C]DASB
DASB
DASB is a compound that binds to the serotonin transporter.Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography since around year 2000....

for serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

s, or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. A novel probe developed at the University of Pittsburgh termed PIB (Pittsburgh compound B
Pittsburgh compound B
Pittsburgh compound B is a fluorescent analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue...

) permits the visualization of amyloid
Amyloid
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...

plaques in the brains of Alzheimer's patients. This technology could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [¹¹C]PMP (N-[¹¹C]methylpiperidin-4-yl propionate) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [¹¹C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for pre-mortem diagnosis of AD and help to monitor AD treatments. Avid Radiopharmaceuticals
Avid Radiopharmaceuticals
Avid Radiopharmaceuticals is an American company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center research campus in Philadelphia, Pennsylvania. The company has developed a radioactive tracer called 18F-AV-45...

of Philadelphia has developed a compound called 18F-AV-45 that uses the longer-lasting radionuclide fluorine-18
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....

to detect amyloid plaques using PET scans.
Neuropsychology
Neuropsychology
Neuropsychology studies the structure and function of the brain related to specific psychological processes and behaviors. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied to efforts to record electrical activity from individual cells in...

/ Cognitive neuroscience
Cognitive neuroscience
Cognitive neuroscience is an academic field concerned with the scientific study of biological substrates underlying cognition, with a specific focus on the neural substrates of mental processes. It addresses the questions of how psychological/cognitive functions are produced by the brain...

: To examine links between specific psychological processes or disorders and brain activity.
Psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...

: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....

s that bind to dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....

s (D1,D2, reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptor
Opioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...

s (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...

, mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s and other psychiatric conditions.

Cardiology

Cardiology is a medical specialty dealing with disorders of the heart . The field includes diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology...

, atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

and vascular disease study: In clinical cardiology

Cardiology

, FDG-PET can identify so-called "hibernating myocardium

Hibernating myocardium

In cardiology, hibernating myocardium is a state when some segmentsof the myocardium exhibit abnormalities of contractile function. Theseabnormalities can be visualised during echocardiography or ventriculography. The finding of a perfusion or metabolic mismatch between PET-FDG and PET-NH3 is...

", but its cost-effectiveness

Cost-effectiveness

Cost-effectiveness analysis is a form of economic analysis that compares the relative costs and outcomes of two or more courses of action. Cost-effectiveness analysis is distinct from cost-benefit analysis, which assigns a monetary value to the measure of effect...

in this role versus SPECT

Single photon emission computed tomography

Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...

is unclear. Recently, a role has been suggested for FDG-PET imaging of atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

to detect patients at risk of stroke

Stroke

A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

http://circ.ahajournals.org/cgi/content/abstract/105/23/2708.

Pharmacology

Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

: In pre-clinical trials, it is possible to radiolabel

Isotopic labeling

Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...

a new drug and inject it into animals. Such scans are referred to as biodistribution studies. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. Much more commonly, however, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an endogenous (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance.

The following is an excerpt from an article by Harvard University

Harvard University

Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

staff writer

Staff writer

Staff writer is a byline that indicates that the author of the article at hand is employed by the periodical that published the article as a regular staff member, and not as a freelance writer or special contributor....

Peter Reuell, featured in HarvardScience

HarvardScience

HarvardScience was a comprehensive, link-rich website featuring news and information about all things relating to science at Harvard University....

, part of the online version of the Harvard Gazette

Harvard Gazette

The Harvard Gazette is the official newspaper of Harvard University, and highlights faculty research, administrative staff, students, and events....

newspaper

Newspaper

A newspaper is a scheduled publication containing news of current events, informative articles, diverse features and advertising. It usually is printed on relatively inexpensive, low-grade paper such as newsprint. By 2007, there were 6580 daily newspapers in the world selling 395 million copies a...

, which discusses research by the team of Harvard Associate Professor of Organic Chemistry

Organic chemistry

Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...

and Chemical Biology

Chemical biology

Chemical biology is a scientific discipline spanning the fields of chemistry and biology that involves the application of chemical techniques and tools, often compounds produced through synthetic chemistry, to the study and manipulation of biological systems. This is a subtle difference from...

Tobias Ritter: "A new chemical process ... may increase the utility of positron emission tomography (PET) in creating real-time

Real-time data

Real-time data denotes information that is delivered immediately after collection. There is no delay in the timeliness of the information provided. Real-time data is often used for navigation or tracking....

3-D images of chemical activity occurring inside the body. This new work ... holds out the tantalizing possibility of using PET scans to peer into a number of functions inside animals and humans by simplifying the process of using “tracer” molecules to create the 3-D images." (by creating a novel electrophilic fluorination reagent as an intermediate molecule; the research could be used in drug development).

Small animal imaging

PET technology for small animal imaging: A miniature PE tomograph has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around. This RatCAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of anesthesia

Anesthesia

Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

. PET scanners designed specifically for imaging rodents or small primates are marketed for academic and pharmaceutical research.

Musculo-skeletal imaging

Musculo-Skeletal Imaging: PET has been shown to be a feasible technique for studying skeletal muscles during exercises like walking. One of the main advantages of using PET is that it can also provide muscle activation data about deeper lying muscles such as the vastus intermedialis and the gluteus minimus, as compared to other muscle studying techniques like Electromyography

Electromyography

Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...

, which can be used only on superficial muscles (i.e., directly under the skin). A clear disadvantage, however, is that PET provides no timing information about muscle activation, because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles.

Safety

PET scanning is non-invasive, but it does involve exposure to ionizing radiation

Ionizing radiation

Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

. The total dose of radiation is significant, usually around 5–7 mSv

Sievert

The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

. However, in modern practice, a combined PET/CT scan is almost always performed, and for PET/CT scanning, the radiation exposure may be substantial - around 23-26 mSv (for a 70 kg person - dose is likely to be higher for higher body weights). When compared to the classification level for radiation workers in the UK of 6 mSv

Sievert

, it can be seen that use of a PET scan need proper justification. This can also be compared to 2.2 mSv average annual background radiation

Background radiation

Background radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....

in the UK

United Kingdom

The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, 0.02 mSv for a chest x-ray and 6.5 - 8 mSv for a CT scan of the chest, according to the Chest Journal and ICRP. A policy change suggested by the IFALPA member associations in year 1999 mentioned that an aircrew member is likely to receive a radiation dose of 4–9 mSv per year.

External links

PET Images Search MedPix(r)
Seeing is believing: In vivo functional real-time imaging of transplanted islets using positron emission tomography (PET)(a protocol), Nature Protocols, from Nature Medicine - 12, 1423 - 1428 (2006).
The nuclear medicine and molecular medicine podcast - Podcast
Positron Emission Particle Tracking (PEPT) - engineering analysis tool based on PET that is able to track single particles in 3D within mixing systems or fluidised beds. Developed at the University of Birmingham, UK.
CMS coverage of PET scans
PET-CT atlas Harvard Medical School
National Isotope Development Center – U.S. Government source of radionuclides including those for PET - production, research, development, distribution, and information

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

History

Description

Operation

Localization of the positron annihilation event

Image reconstruction using coincidence statistics

Combination of PET with CT or MRI

Radionuclides

Limitations

Image reconstruction

Applications

Oncology

Neuroimaging

Cardiology

Pharmacology

Small animal imaging

Musculo-skeletal imaging

Safety

See also

External links