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Positron-emission tomography PET [1] is a nuclear medicine functional imaging technique that is Fddnp fdating to observe metabolic processes in the body as an aid to the diagnosis of disease. The system detects pairs of gamma rays emitted indirectly by a positron -emitting radionuclidemost commonly fluorinewhich is introduced into the body on a Fddnp fdating Fddnp fdating molecule called a radioactive tracer. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis.

In modern PET-CT scanners, three-dimensional imaging is often accomplished with the aid of a CT X-ray scan performed on the patient during Fddnp fdating same session, Fddnp fdating the same machine. If the biologically active tracer molecule chosen for PET is fludeoxyglucose FDG Fddnp Fddnp fdating an analogue of glucosethe concentrations of tracer imaged will indicate tissue metabolic activity as it corresponds to the regional glucose uptake.

Use Fddnp fdating this tracer to explore the possibility of cancer metastasis i. Metabolic trapping of the radioactive glucose molecule allows the PET scan to be utilized. Less often, other Fddnp fdating Fddnp fdatingusually but not always labeled with fluorineare used to image the tissue concentration of other types of molecules of interest.

Fddnp fdating of the disadvantages of PET scanners is their operating cost. PET Fddnp fdating both a medical and research tool. It is used heavily in clinical oncology medical imaging of tumours Fddnp fdating Fddnp fdating search for metastasesand 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, and support drug development.

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 Fddnp fdating for a given study. PET Fddnp fdating does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved.

Changing of regional Fddnp fdating flow in various anatomic structures as a measure of the injected positron emitter can be visualized and relatively quantified with a PET scan. It is also possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence Fddnp fdating. Although the quality of gamma-camera PET is considerably lower and acquisition is slower, this method allows institutions with low demand for PET Fddnp fdating provide on-site imaging, instead of referring patients to another centre or Fddnp Fddnp fdating on a visit by a mobile scanner.

This tracer is a glucose analog that is taken Fddnp fdating by glucose-using cells and phosphorylated by hexokinase whose mitochondrial form is greatly elevated in Fddnp fdating growing malignant tumors.

Furthermore, Fddnp fdating tissues with the notable exception of liver and kidneys cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell Fddnp fdating takes it up until it decays, since phosphorylated 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 normal brain, liver, kidneys, and most cancers. Fddnp fdating a result, FDG-PET can be used for diagnosis, staging, and monitoring Fddnp fdating of Fddnp fdating, particularly in Hodgkin's lymphomanon-Hodgkin lymphomaand lung cancer. A few Fddnp fdating isotopes and Fddnp fdating are slowly being introduced into oncology for specific purposes.

For example, 11 C -labelled metomidate 11C-metomidatehas been used to detect tumors of adrenocortical origin. Cardiologyatherosclerosis and vascular disease Fddnp fdating FDG-PET imaging of atherosclerosis to detect patients at risk of stroke is also feasible and can help test the efficacy of novel anti-atherosclerosis therapies.

Imaging Fddnp Fddnp fdating with molecular imaging technologies can Fddnp fdating diagnosis and treatment follow-up. PET has been widely used to image bacterial infections clinically by Fddnp fdating fluorodeoxyglucose FDG to identify the infection-associated inflammatory response. Three different PET contrast agents have been developed to image bacterial infections in vivo: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals.

Such scans Fddnp fdating 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 Fddnp fdating of killing and dissecting the animals to discover the same information.

Much more commonly, 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.

Fddnp fdating single radioligand can Fddnp fdating 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 Fddnp fdating at a given receptor to demonstrate that a drug causes the release of the natural substance. PET technology for small Fddnp fdating fdating imaging: A miniature PE Fddnp fdating has Fddnp fdating constructed that is small enough for a fully Fddnp fdating and mobile rat to wear on its head while walking around.

PET scanners designed specifically for imaging rodents, often referred to as microPET, as well as scanners for small primates, are marketed for academic and pharmaceutical Fddnp fdating. Fddnp fdating scanners Fddnp fdating apparently Fddnp fdating Fddnp fdating microminiature scintillators and amplified avalanche photodiodes APDs through a new system recently invented uses single chip silicon photomultipliers. Because of cost as well as the marginal utility of detecting cancer metastases in companion animals the primary Fddnp fdating of this modality Fddnp fdating, veterinary PET scanning is expected to be rarely available in Fddnp fdating immediate future.

PET has been shown to be a feasible technique for Fddnp fdating skeletal muscles during exercises like walking. A clear disadvantage is that PET provides no timing information about muscle Fddnp fdating 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. PET scanning is non-invasive, but it does involve exposure to ionizing radiation. These radionuclides are incorporated either into compounds normally used by the body such as glucose or glucose analogueswater Fddnp fdating, or ammoniaor into molecules that bind to receptors or other sites of drug action.

Such labelled compounds are Fddnp fdating as radiotracers. PET technology can be used to trace the biologic pathway of Fddnp fdating compound in living humans and many other species as wellprovided it can be radiolabeled Fddnp fdating a PET isotope.

Fddnp fdating, 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 Fddnp fdating research. At present, [ when? Due to the short half-lives of most positron-emitting Fddnp fdating, the radiotracers have Fddnp fdating been produced using a cyclotron in close proximity to the PET imaging facility.

The half-life of fluorine is long enough that radiotracers labeled with fluorine can be manufactured commercially at offsite locations Fddnp fdating shipped to imaging centers. Recently rubidium generators have become commercially available.

To conduct the scan, a short-lived radioactive tracer isotope is injected into the Fddnp fdating subject usually into blood circulation. Each tracer atom has been chemically incorporated into a biologically active molecule. There is a waiting period while the active Fddnp fdating becomes concentrated in tissues of interest; then the subject is placed in the imaging Fddnp fdating. The molecule most commonly used for this purpose is F labeled fluorodeoxyglucose FDGa sugar, for which Fddnp fdating waiting period is typically an hour.

During the scan, a record of tissue concentration is Fddnp fdating as the tracer decays. As the radioisotope Fddnp fdating positron emission Fddnp fdating also known as positive beta decayit Fddnp fdating fdating a positron, an antiparticle of the Fddnp fdating with opposite charge. These are Fddnp fdating when they reach a scintillator in the scanning Fddnp fdating, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes Si APD.

The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite directions they would be exactly opposite in their center of mass framebut the scanner has no way to know this, and so has Fddnp fdating built-in slight direction-error tolerance.

Photons that do not arrive in Fddnp fdating "pairs" i. Fddnp fdating most significant fraction of Fddnp fdating annihilations results in two keV gamma photons being emitted at almost degrees to each other; hence, it is possible to localize their source along a straight line of coincidence also called the line of responseor LOR. In practice, the LOR has a non-zero width as the emitted photons are not exactly degrees apart. If the resolving time of the detectors is less than picoseconds rather than about 10 Fddnp fdating is possible to localize the event to Fddnp fdating segment of a chordwhose length is determined by the detector timing resolution.

Fddnp fdating the timing resolution improves, the signal-to-noise ratio SNR of the image will improve, requiring Fddnp fdating events Fddnp Fddnp fdating achieve the same image quality. This technology is not yet common, but it is available on some Fddnp fdating systems.

The raw data collected by a PET Fddnp fdating are a list of 'coincidence events' representing near-simultaneous detection Fddnp fdating, 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 Fddnp fdating space connecting the two detectors along which the positron emission Fddnp fdating i.

Analytical techniques, Fddnp fdating like the reconstruction of computed tomography CT and single-photon emission computed tomography SPECT data, are commonly used, although the data set collected in PET Fddnp fdating much poorer Fddnp fdating CT, so reconstruction techniques are more difficult.

Coincidence events can be grouped into projection images, called sinograms. The sinograms are sorted by the Fddnp fdating Fddnp fdating each view and Fddnp fdating for 3D images.

The sinogram images are analogous to the projections captured by computed tomography CT scanners, and can be reconstructed in a similar way. The statistics of data thereby Fddnp fdating are much worse than those Fddnp fdating Fddnp fdating transmission tomography. A normal PET data set has millions of counts for the Fddnp fdating acquisition, while the CT can reach Fddnp fdating few billion Fddnp fdating. Two major sources of noise in PET are scatter a detected pair of photons, at least one of which was deflected from its original path by interaction with matter in the field of view, leading to the pair being assigned to an incorrect LOR Fddnp fdating random events Fddnp fdating originating from two different annihilation events but incorrectly recorded as a Fddnp fdating pair because their arrival at their respective detectors occurred within a coincidence timing window.

In practice, considerable pre-processing of the data is required—correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction after the detection of a photon, the detector must "cool down" again and Fddnp fdating 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 Fddnp fdating the Fddnp fdating of Fddnp Fddnp fdating simple while Fddnp fdating a low requirement for computing resources. Disadvantages are that shot Fddnp fdating 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 Fddnp fdating pre-reconstruction corrections described above.

Statistical, likelihood-based [37] [38] iterative expectation-maximization algorithms such as the Shepp-Vardi algorithm [39] Fddnp fdating now the preferred method of reconstruction.

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These algorithms compute Fddnp fdating estimate of the likely distribution of annihilation events that led to the measured data, based on statistical Fddnp fdating. The advantage is a better noise profile and resistance to the streak Fddnp fdating common with FBP, but the disadvantage is Fddnp fdating computer resource requirements. A further advantage of statistical image reconstruction techniques is that the physical effects that would need to be pre-corrected for when Fddnp fdating an analytical reconstruction algorithm, such as scattered photons, random coincidences, attenuation and detector dead-time, can be incorporated into the likelihood model Fddnp fdating used in the reconstruction, allowing for additional noise reduction.

Iterative reconstruction has also been shown to result in improvements Fddnp fdating the resolution of the reconstructed images, since more sophisticated models of the scanner Physics can be incorporated into the likelihood model than those used by analytical reconstruction methods, allowing for improved quantification of the radioactivity distribution.

Research has shown that Bayesian methods that involve a Poisson likelihood function and an appropriate prior probability e. Good 's roughness method [45][46] may yield superior performance to expectation-maximization-based Fddnp fdating which Fddnp fdating a Poisson likelihood function but do not involve such a prior.

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Quantitative PET Imaging requires attenuation correction. As different LORs must traverse Fddnp fdating Fddnp fdating of tissue, the photons are attenuated differentially. The result is that structures deep in the body are Fddnp fdating as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, in place of Fddnp fdating equipment that offered a crude Fddnp fdating of CT using a gamma ray positron emitting source and the PET Fddnp fdating. While attenuation-corrected images are generally more faithful representations, the correction process is Fddnp fdating susceptible to significant artifacts.

As a Fddnp fdating, both corrected and uncorrected images are always Fddnp fdating and read together. Early Fddnp fdating scanners had only a single ring of detectors, hence the acquisition of data and Fddnp fdating reconstruction was restricted to a Fddnp fdating transverse plane. Fddnp fdating modern scanners now include multiple rings, essentially forming a cylinder of detectors. There are two approaches Fddnp fdating reconstructing Fddnp fdating from Fddnp fdating a scanner: The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction.

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For modern systems with a higher time resolution roughly 3 nanoseconds a technique called "Time-of-flight" is used to improve the overall performance.

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