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| {{mergefrom|PET-CT|date=August 2013}}
| | == just two back == |
| {{mergefrom|PET-MRI|date=August 2013}}
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| {{Infobox interventions
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| | Name = Positron Emission Tomography
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| | Image = ECAT-Exact-HR--PET-Scanner.jpg
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| | Caption = Image of a typical positron emission tomography (PET) facility
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| | ICD10 = C?3
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| | ICD9 = {{ICD9proc|92.0}}-{{ICD9proc|92.1}}
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| | MeshID = D049268
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| | MedlinePlus = 003827
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| | OPS301 = {{OPS301|3-74}}
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| | OtherCodes =
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| }}
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| [[File:16slicePETCT.jpg|thumb|250px|PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent]]
| | The sky, Xiao Yan Emperor and soul up to lofty-like body that is void marching backwards a few steps, each step down, there are a few little knowledge [http://www.ispsc.edu.ph/nav/japandi/casio-rakuten-8.html カシオ 掛け時計] of space burst into a dark nothingness.<br><br>However, just two back, in turn is [http://www.ispsc.edu.ph/nav/japandi/casio-rakuten-0.html カシオ電波ソーラー腕時計] a storm washed out, this battle is not extremely brilliant, but it is strong to extreme forces collide, no one can imagine, when the two behemoths fight with lofty metering When, that is how have the visual impact.<br>collision [http://alleganycountyfair.org/sitemap.xml http://alleganycountyfair.org/sitemap.xml] between<br>, FY shock, thunder flashes, as if heaven [http://www.ispsc.edu.ph/nav/japandi/casio-rakuten-11.html カシオ ソーラー電波腕時計] and earth, are in for this and other encounters and trembling.<br><br>two behemoths battle, for the Central Plains, this is obviously caused great damage upon the earth, constantly shaking violently, huge cracks in the abyss, almost to the Central Plains into two, all creatures, In this and so are fighting hard [http://www.ispsc.edu.ph/nav/japandi/casio-rakuten-12.html 時計 カシオ] work, just that the aftermath of a minor, a fighting holy enough to be strong |
| [[File:PET-MIPS-anim.gif|thumb|Whole-body PET scan using <sup>18</sup>F-FDG]]
| | 相关的主题文章： |
| | | <ul> |
| '''Positron emission tomography''' ('''PET''')<ref>{{cite book
| | |
| | title = Positron Emission Tomography: Basic Sciences
| | <li>[http://www.cnklc.com/plus/feedback.php?aid=91 http://www.cnklc.com/plus/feedback.php?aid=91]</li> |
| | last = Bailey
| | |
| | first = D.L
| | <li>[http://www.zgsjyxpt.net/plus/feedback.php?aid=4999 http://www.zgsjyxpt.net/plus/feedback.php?aid=4999]</li> |
| | coauthors = D.W. Townsend, P.E. Valk, M.N. Maisey
| | |
| | year = 2005 | url=http://www.springer.com/?SGWID=0-102-24-0-0&searchType=EASY_CDA&queryText=Positron+Emission+Tomography%3A+Basic+Sciences
| | <li>[http://www.52zju.com/home.php?mod=space&uid=454071 http://www.52zju.com/home.php?mod=space&uid=454071]</li> |
| | publisher = Springer-Verlag
| | |
| | place = Secaucus, NJ
| | </ul> |
| | isbn = 1-85233-798-2
| |
| }}</ref> is a [[nuclear medicine]], [[functional imaging]] technique that produces a three-dimensional image of functional processes in the body. The system detects pairs of [[gamma ray]]s emitted indirectly by a [[positron]]-emitting [[radionuclide]] ([[radioactive tracer|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 [[PET-CT]] scanners, three dimensional imaging is often accomplished with the aid of a [[Computed tomography|CT X-ray scan]] performed on the patient during the same session, in the same machine.
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| If the biologically active molecule chosen for PET is [[fludeoxyglucose]] (FDG), an [[structural analog|analogue]] of [[glucose]], the concentrations of tracer imaged will indicate tissue metabolic activity by virtue of the regional glucose uptake. Use of this tracer to explore the possibility of [[cancer]] [[metastasis]] (i.e., spreading to other sites) is the most common type of PET scan in standard medical care (90% of current scans). However, on a minority basis, many other [[radioactive tracers]] are used in PET to image the tissue concentration of many other types of molecules of interest.
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| == History ==
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| The concept of emission and transmission [[tomography]] was introduced by [[David E. Kuhl]], 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]]. Tomographic imaging techniques were further developed by [[Michel Ter-Pogossian]], [[Michael E. Phelps]] and others at [[Washington University School of Medicine]].<ref>{{cite journal
| |
| | title = A positron-emission transaxial tomograph for nuclear imaging (PET)
| |
| | last = Ter-Pogossian
| |
| | first = M.M.
| |
| | coauthors = M.E. Phelps, E.J. Hoffman, N.A. Mullani
| |
| | journal = [[Radiology (journal)|Radiology]]
| |
| | volume = 114
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| | issue = 1
| |
| | pages = 89–98
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| | year = 1975
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| | osti = 4251398
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| | pmid = 1208874
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| }}</ref><ref>{{cite journal
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| | title = Application of annihilation coincidence detection to transaxial reconstruction tomography
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| | last = Phelps
| |
| | first = M.E.
| |
| | coauthors = E.J. Hoffman, N.A. Mullani, M.M. Ter-Pogossian
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| | journal = [[Journal of Nuclear Medicine]]
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| | volume = 16
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| | issue = 3
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| | pages = 210–224
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| | date = March 1, 1975 | url=http://jnm.snmjournals.org/cgi/content/abstract/16/3/210
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| | pmid = 1113170
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| }}</ref>
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| Work by Gordon Brownell, Charles Burnham and their associates at the [[Massachusetts General Hospital]] beginning in the 1950s contributed significantly to the development of PET technology and included the first demonstration of annihilation radiation for medical imaging.<ref>{{cite journal
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| | title = Localization of brain tumors with positron emitters
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| | last = Sweet
| |
| | first = W.H.
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| | coauthors = G.L. Brownell
| |
| | journal = [[Nucleonics]]
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| | volume = 11
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| | pages = 40–45
| |
| | year = 1953
| |
| }}</ref> 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."<ref>''A Vital Legacy: Biological and Environmental Research in the Atomic Age,'' U.S. Department of Energy, The Office of Biological and Environmental Research, September 2010, p 25–26</ref>
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| 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.<ref>IDO, T., C-N. WAN, V. CASELLA, J.S. FOWLER, A.P. WOLF, M. REIVICH, and D.E. KUHL, ''Labeled 2-deoxy-D-glucose analogs. -labeled 2-deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and C-14-2-deoxy-2-fluoro-D-glucose'', The Journal of Labelled Compounds and Radiopharmaceuticals 1978; 14:175-182.</ref> The compound was first administered to two normal human volunteers by [[Abass Alavi]] 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.
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| 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.<ref>BROWNELL G.L., Dave Marcum, B. HOOP JR., and D.E. BOHNING, "Quantitative dynamic studies using short-lived radioisotopes and positron detection" in Proceedings of the Symposium on Dynamic Studies with Radioisotopes in Medicine, Rotterdam. August 31–September 4, 1945. IAEA. Vienna. 194824. pp. 161–172.</ref> 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<ref>ROBERTSON J.S., MARR R.B., ROSENBLUM M., RADEKA V., and YAMAMOTO Y.L., ``32-Crystal positron transverse section detector'', in Tomographic Imaging in Nuclear Medicine, Freedman GS, Editor. 1983, The Society of Nuclear Medicine: New York. pp. 142–153.</ref> and [[Zang-Hee Cho]]<ref>CHO, Z. H., ERIKSSON L., and CHAN J.K., ``A circular ring transverse axial positron camera'' in Reconstruction Tomography in Diagnostic Radiology and Nuclear Medicine, Ed. Ter-Pogossian MM., University Park Press: Baltimore, 1975.</ref> were the first to propose a ring system that has become the prototype of the current shape of PET.
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| 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.<ref>{{cite web|url=http://www.petscaninfo.com/zportal/portals/phys/petct/history |title=PET Scan: PET/CT History |publisher=Petscaninfo.com |date= |accessdate=2012-08-13}}</ref>
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| == Descriptions ==
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| [[File:PET-detectorsystem 2.png|thumb|Schematic view of a detector block and ring of a PET scanner]]
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| === Operation ===
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| To conduct the scan, a short-lived [[radioactivity|radioactive]] tracer [[isotope]] is injected into the living subject (usually into [[blood]] 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]] (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.
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| [[File:PET-schema.png|thumb|200px|right|Schema of a PET acquisition process]]
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| As the radioisotope undergoes [[positron emission]] decay (also known as positive [[beta decay]]), it emits a positron, an antiparticle of the [[electron]] with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on the isotope<ref>{{cite book | title=PET: physics, instrumentation, and scanners|author=Michael E. Phelps|publisher=Springer|year=2006|pages=8–10 | isbn=0-387-34946-4}}</ref>), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron.<ref>{{cite web |archivedate=2012-02-05|archiveurl=http://web.archive.org/web/20120205102047/http://www.medcyclopaedia.com/library/topics/volume_i/p/pet_imaging.aspx|url=http://www.medcyclopaedia.com/library/topics/volume_i/p/pet_imaging.aspx|title=PET Imaging |publisher=GE Healthcare}}</ref> The encounter annihilates both electron and positron, producing a pair of [[electron–positron annihilation|annihilation]] ([[gamma ray|gamma]]) [[photon]]s moving in approximately opposite directions. These are detected when they reach a [[scintillator]] in the scanning device, creating a burst of light which is detected by [[photomultiplier]] tubes or silicon [[avalanche photodiode]]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.
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| === Localization of the positron annihilation event ===
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| The most significant fraction of electron–positron annihilations results 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 non-zero 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 (geometry)|chord]], whose length is determined by the detector timing resolution. As the timing resolution improves, the [[signal-to-noise ratio]] (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.<ref>{{cite web |url=http://www.uphs.upenn.edu/news/News_Releases/jun06/PETCTITC.htm |title=Invitation to Cover: Advancements in "Time-of-Flight" Technology Make New PET/CT Scanner at Penn a First in the World |date=June 15, 2006 |accessdate=February 22, 2010 |publisher=University of Pennsylvania}}</ref>
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| === Image reconstruction using coincidence statistics ===
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| A technique much like the reconstruction of [[computed tomography]] (CT) and [[single-photon emission computed tomography]] (SPECT) data is more commonly used, although the [[data set]] collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see [[#Image reconstruction|Image reconstruction]] of PET).
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| 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]]s) can 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]] or [[radiologist]] in the context of the patient's diagnosis and treatment plan.
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| [[File:Viewer medecine nucleaire keosys.JPG|thumb|keosys|200px|left|A complete body PET / CT Fusion image]]
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| [[File:PET-MR2-Head-Keosys.JPG|thumb|keosys|200px|right|A Brain PET / MRI Fusion image]]
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| === Combination of PET with CT or MRI ===
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| {{Main|PET-CT|PET-MRI}}
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| PET scans are increasingly read alongside CT or [[magnetic resonance imaging]] (MRI) scans, with the combination (called [[Image registration|"co-registration"]]) 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 (so-called "PET-CT"). 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 [[image registration|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.
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| At the [[Forschungszentrum Jülich|Jülich]] Institute of Neurosciences and Biophysics, the world's largest PET-MRI device began operation in April 2009: a 9.4-[[Tesla (unit)|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.<ref name="PET_MRT">{{cite news | title = A Close Look Into the Brain | publisher = [[Jülich Research Centre]] | date = 31 March 2011 | accessdate = 2011-03-31 | url = http://www2.fz-juelich.de/portal/research/health/9-4-mr-pet}}</ref>
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| === Radionuclides and radiotracers ===
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| {{main|List of PET radiotracers|Fludeoxyglucose}}
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| [[Radionuclide]]s used in PET scanning are typically [[isotope]]s with short [[half-life|half-lives]] such as [[carbon-11]] (~20 min), [[nitrogen-13]] (~10 min), [[oxygen-15]] (~2 min), [[fluorine-18]] (~110 min)., or [[Isotopes of rubidium#Rubidium-82|rubidium-82]](~1.27 min). These radionuclides are incorporated either into compounds normally used by the body such as [[glucose]] (or glucose analogues), [[water]], or [[ammonia]], or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as [[radiotracer]]s. 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 [[fluorodeoxyglucose]] (also called FDG or fludeoxyglucose), an analogue of glucose that is labeled with fluorine-18. This radiotracer is used in essentially all scans for oncology and most scans in neurology, and thus makes up the large majority of all of the radiotracer (> 95%) used in PET and PET-CT scanning.
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| Due to the short half-lives of most positron-emitting radioisotopes, the radiotracers have traditionally been produced using a [[cyclotron]] 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]]-82 generators have become commercially available.<ref>Bracco Diagnostics, [http://www.nuclearonline.org/PI/Cardiogen.pdf CardioGen-82], 2000</ref> These contain strontium-82, which decays by [[electron capture]] to produce positron-emitting rubidium-82.
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| === Limitations ===
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| 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,<ref>{{cite journal | author=Young H | title=Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations| journal=European Journal of Cancer| volume=35 | issue=13 | year=1999| pages=1773–1782 | doi = 10.1016/S0959-8049(99)00229-4 | pmid=10673991 | author-separator=, | author2=Baum R | author3=Cremerius U | display-authors=3 | last4=Herholz | first4=K. | last5=Hoekstra | first5=O. | last6=Lammertsma | first6=A.A. | last7=Pruim | first7=J. | last8=Price | first8=P.}}</ref> where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.
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| 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 after radioisotope preparation. Organic radiotracer molecules that will contain a positron-emitting radioisotope cannot be synthesized first and then the radioisotope prepared within them, because bombardment with a cyclotron to prepare the radioisotope destroys any organic carrier for it. Instead, the isotope must be prepared first, then afterward, the chemistry to prepare any organic radiotracer (such as [[Fludeoxyglucose (18F)|FDG]]) accomplished very quickly, in the short time before the isotope decays. 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 [[Isotopes of rubidium|rubidium-82]] (used as [[rubidium-82 chloride]]) with a half-life of 1.27 minutes, which is created in a portable generator and is used for [[myocardium|myocardial]] [[perfusion]] studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and "hot labs" (automated chemistry labs that are able to work with radioisotopes) 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<ref>[http://www.medicalimagingmag.com/issues/articles/2003-07_05.asp Technology | July 2003: Trends in MRI | Medical Imaging<!-- Bot generated title -->]</ref>
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| 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.
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| === Image reconstruction ===
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| 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 (i.e., the line of response (LOR)). 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.
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| Coincidence events can be grouped into projection images, called [[Computed axial tomography|sinograms]]. 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]] (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.
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| In practice, considerable pre-processing of the data is required—correction for random coincidences, estimation and subtraction of [[compton scatter|scattered]] photons, detector [[Dead time|dead-time]] 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).
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| [[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]] 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.
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| Iterative [[expectation-maximization algorithm]]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.<ref>{{cite journal|last=Vardi|first=Y.|coauthors=L. A. Shepp, and L. Kaufman|title=A statistical model for positron emission tomography|journal=Journal of the American Statistical Association|year=1985|volume=80|pages=8–37}}</ref>
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| Recent research has shown that [[Bayesian probability|Bayesian]] methods that involve a Poisson likelihood function and an appropriate prior (e.g., a smoothing prior leading to [[total variation regularization]] or a [[Laplace distribution|Laplacian prior]] leading to <math>\ell_1</math>-based regularization in a [[wavelet]] or other domain) may yield superior performance to expectation-maximization-based methods which involve a Poisson likelihood function but do not involve such a prior.<ref>{{cite journal|last=Willett|first=R.|coauthors=Z. Harmany, R. Marcia|title=Poisson Image Reconstruction with Total Variation Regularization|journal=Accepted to IEEE International Conference on Image Processing (ICIP)|year=2010}}</ref><ref>{{cite journal|last=Harmany|first=Z.|coauthors=R. Marcia, R. Willett|title=Sparsity-regularized Photon-limited Imaging|journal=International Symposium on Biomedical Imaging (ISBI)|year=2010}}</ref><ref>{{cite journal|last=Harmany|first=Z.|coauthors=R. Marcia, R. Willett|title=SPIRAL out of Convexity: Sparsity-regularized Algorithms for Photon-limited Imaging|journal=SPIE Electronic Imaging|year=2010}}</ref>
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| '''Attenuation correction''': Attenuation occurs when [[photon]]s emitted by the radiotracer inside the body are absorbed by intervening tissue between the detector and the emission of the photon. As different LORs must traverse different thicknesses of tissue, the photons 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]] CT equipment, however earlier equipment offered a crude form of CT using a [[gamma ray]] ([[positron]] emitting) source and the PET detectors.
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| 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.
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| '''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.
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| 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).
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| 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.
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| == Applications ==
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| PET is both a medical and research tool. It is used heavily in clinical [[oncology]] ([[radiology|medical imaging]] of [[tumor]]s and the search for [[metastasis|metastases]]), 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, and support drug development.
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| 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.
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| Alternative methods of scanning include [[x-ray]] [[computed tomography]] (CT), [[magnetic resonance imaging]] (MRI) and [[functional magnetic resonance imaging]] (fMRI), [[ultrasound]] and [[single-photon emission computed tomography]] (SPECT).
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| 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]] 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.
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| 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]] 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.
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| PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.
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| ===Oncology===
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| [[Oncology]]: PET scanning with the tracer [[fluorine-18]] (F-18) [[fluorodeoxyglucose]] (FDG), called FDG-PET, is widely used in clinical [[oncology]]. This tracer is a [[glucose]] [[analog (chemistry)|analog]] that is taken up by glucose-using cells and phosphorylated by [[hexokinase]] (whose [[mitochondrial]] form is greatly elevated in rapidly growing [[malignant]] tumours). A typical dose of FDG used in an oncological scan is 200–400 M[[Becquerel|Bq]] for an adult human. Because the [[oxygen]] atom that is replaced by F-18 to generate FDG is required for the next step in glucose [[metabolism]] in all cells, no further reactions occur in FDG. Furthermore, most 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 that takes it up, until it decays, since [[phosphorylation|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 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]], [[non-Hodgkin lymphoma]], and [[lung cancer]]. 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]], 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]] (CT) and [[magnetic resonance imaging]] (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper [[health technology assessment]]; 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.
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| A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, {{anchor|Metomidate}}11C-Metomidate has been used to detect tumors of [[adrenocortical]] origin.<ref>{{cite pmid|12634969}}</ref><ref>{{cite journal |author=Minn H |title=Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG |journal=J. Nucl. Med. |volume=45 |issue=6 |pages=972–9 | date=June 2004 |pmid=15181132 |doi= |url=http://jnm.snmjournals.org/cgi/content/full/45/6/972 |author-separator=, |author2=Salonen A |author3=Friberg J |display-authors=3 |last4=Roivainen |first4=A |last5=Viljanen |first5=T |last6=Långsjö |first6=J |last7=Salmi |first7=J |last8=Välimäki |first8=M |last9=Någren |first9=K}}</ref> Also, [[FDOPA]] PET-CT, in centers which offer it, has proven to be a more sensitive alternative to finding, and also localizing [[pheochromocytoma]] than the [[MIBG scan]].<ref>[http://hyper.ahajournals.org/content/38/1/6.full] full text of early article on FDOPA PET for pheochromocytoma</ref><ref>[http://emedicine.medscape.com/article/379861-overview] imaging overview</ref><ref>Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Clinical value of (18)F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ((18)F-DOPA PET/CT) for detecting pheochromocytoma. Eur J Nucl Med Mol Imaging. Oct 28 2009</ref>
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| ===Neuroimaging===
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| {{main|Brain positron emission tomography}}
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| # [[File:PET-image.jpg|thumb|200px|right|PET scan of the [[human brain]].]] [[Neurology]]: PET [[neuroimaging]] 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]]-15. However, because of its 2-minute half-life, O-15 must be piped directly from a medical [[cyclotron]] 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]] 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 [[radiotracer]]s (i.e. [[radioligand]]s) have been developed for PET that are [[ligand (biochemistry)|ligands]] for specific [[neuroreceptor]] subtypes such as [<sup>11</sup>C] [[raclopride]] and [<sup>18</sup>F] [[fallypride]] for [[dopamine]] D2/D3 receptors, [<sup>11</sup>C] [[McN 5652]] and [<sup>11</sup>C] [[DASB]] for [[serotonin transporter]]s, or enzyme substrates (e.g. 6-[[FDOPA]] for the [[Aromatic L-amino acid decarboxylase|AADC enzyme]]). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[<sup>18</sup>F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([<sup>18</sup>F]FDDNP)<ref>{{cite journal | title=Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease| author=E. D. Agdeppa, V. Kepe, J. Liu, S. Flores-Torres, N. Satyamurthy, A. Petric, G. M. Cole, G. W. Small, S.-C. Huang, and J. R. Barrio| journal=J Neurosci. | url = http://www.jneurosci.org/content/21/24/RC189.full.pdf | volume = 21 | pages = RC189(1–5) | year=2001|pmid=11734604}}</ref> developed at the University of California, Los Angeles and N-methyl-[<sup>11</sup>C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole<ref>{{cite journal | title=A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain| author=C. A. Mathis, B. J. Bacskai, S. T. Kajdasz, M. E. McLellan, M. P. Frosch, B. T. Hyman, D. P. Holt, Y. Wang, G.-F. Huang, M. L. Debnath, and W. E. Klunk | journal=Bioorganic Med Chem Lett. | doi=10.1016/S0960-894X(01)00734-X | volume=12 | pages=295–298 | year=2002}}</ref> (termed [[Pittsburgh compound B]]) developed at the University of Pittsburgh. These amyloid imaging probes permit the visualization of [[amyloid]] plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [<sup>11</sup>C]PMP (N-[<sup>11</sup>C]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. [<sup>11</sup>C]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.<ref>{{cite journal |author=Kuhl DE, Koeppe RA, Minoshima S, ''et al.'' |title=In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease |journal=Neurology |volume=52 |issue=4 |pages=691–9 | date=March 1999 |pmid=10078712 |doi= |url=}}</ref> [[Avid Radiopharmaceuticals]] of [[Philadelphia]] has developed a compound called 18F-AV-45 that uses the longer-lasting radionuclide [[fluorine-18]] to detect amyloid plaques using PET scans.<ref>[[Gina Kolata|Kolata, Gina]]. [http://www.nytimes.com/2010/06/24/health/research/24scans.html "Promise Seen for Detection of Alzheimer’s"], ''[[The New York Times]]'', June 23, 2010. Accessed June 23, 2010.</ref>
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| # [[Neuropsychology]] / [[Cognitive neuroscience]]: To examine links between specific psychological processes or disorders and brain activity.
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| # [[Psychiatry]]: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. [[Radioligand]]s that bind to [[dopamine receptor]]s (D1,<ref>{{cite journal | title=Imaging cortical dopamine D1 receptors using 11C NNC112 and ketanserin blockade of the 5-HT 2A receptors | author=Catafau AM, Searle GE, Bullich S, Gunn RN, Rabiner EA, Herance R, Radua J, Farre M, Laruelle M. | journal=J Cereb Blood Flow Metab | url=http://www.nature.com/jcbfm/journal/v30/n5/full/jcbfm2009269a.html | volume = 30 | pages = 985–93 | year=2010}}</ref> D2, reuptake transporter), [[serotonin receptor]]s (5HT1A, 5HT2A, reuptake transporter) [[opioid receptor]]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]], [[substance abuse]], [[mood disorder]]s and other psychiatric conditions.
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| ===Cardiology===
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| {{main|Cardiac PET}}
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| [[Cardiology]], [[atherosclerosis]] and vascular disease study: In clinical [[cardiology]], FDG-PET can identify so-called "[[hibernating myocardium]]", but its [[cost-effectiveness]] in this role versus [[single photon emission computed tomography|SPECT]] is unclear. 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.<ref>{{cite web|url=http://circ.ahajournals.org/cgi/content/abstract/105/23/2708 |title=Imaging Atherosclerotic Plaque Inflammation With [18F]-Fluorodeoxyglucose Positron Emission Tomography |publisher=Circ.ahajournals.org |date=2002-05-20 |accessdate=2012-08-13}}</ref><ref>{{cite web|url=http://www.plaqueimaging.com/plaque-imaging/tag/pet|title=Plaque Imaging with FDG PET|accessdate=2013-02-07}}</ref>
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| ===Pharmacokinetics===
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| [[Pharmacokinetics]]: In pre-clinical trials, it is possible to [[isotopic labeling|radiolabel]] 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.
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| The following is an excerpt from an article by [[Harvard University]] [[staff writer]] Peter Reuell, featured in [[HarvardScience]], part of the online version of the [[Harvard Gazette]] [[newspaper]], which discusses research by the team of Harvard [[Associate Professor]] of [[Organic Chemistry]] and [[Chemical Biology]] [[Tobias Ritter]]: "A new chemical process ... may increase the utility of positron emission tomography (PET) in creating [[Real-time data|real-time]] [[3D computer graphics|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).<ref>{{cite web|url=http://news.harvard.edu/gazette/story/2011/11/tracing-biological-pathways/ |title=Tracing biological pathways | Harvard Gazette |publisher=News.harvard.edu |date= |accessdate=2012-08-13}}</ref>
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| ===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.<ref>[http://www.chemistry.bnl.gov/ratcap/gallery.html Rat Conscious Animal PET]</ref> This RatCAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of [[anesthesia]]. 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 research.
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| ===Musculo-skeletal imaging===
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| [[Musculo-Skeletal Imaging]]: PET has been shown to be a feasible technique for studying skeletal muscles during exercises like walking.<ref>{{cite journal |author=Oi N, Iwaya T, Itoh M, Yamaguchi K, Tobimatsu Y, Fujimoto T |title=FDG-PET imaging of lower extremity muscular activity during level walking |journal=J Orthop Sci |volume=8 |issue=1 |pages=55–61 |year=2003 |pmid=12560887 |doi=10.1007/s007760300009 |url=}}</ref> 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]], 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.
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| == Safety ==
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| PET scanning is non-invasive, but it does involve exposure to [[ionizing radiation]]. The total dose of radiation is significant, usually around 5–7 m[[Sievert|Sv]]. 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).<ref>{{cite journal |author=Brix G, Lechel U, Glatting G, ''et al.'' |title=Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations |journal=J. Nucl. Med. |volume=46 |issue=4 |pages=608–13 | date=April 2005 |pmid=15809483 |doi= |url=}}</ref> When compared to the classification level for radiation workers in the UK of 6 m[[Sievert|Sv]], it can be seen that use of a PET scan needs proper justification.{{Citation needed|date=September 2011}} This can also be compared to 2.2 mSv average annual [[background radiation]] in the [[United Kingdom|UK]], 0.02 mSv for a chest x-ray and 6.5–8 mSv for a CT scan of the chest, according to the journal ''[[Chest (journal)|Chest]]'' and ICRP.<ref>[https://web.archive.org/web/20051015024328/http://www.icrp.org/downloadDoc.asp?document=docs/ICRP_87_CT_s.pps], [[ICRP]], 30 October 2009.</ref><ref>{{cite journal |author=de Jong PA, Tiddens HA, Lequin MH, Robinson TE, Brody AS |title=Estimation of the radiation dose from CT in cystic fibrosis |journal=Chest |volume=133 |issue=5 |pages=1289–91; author reply 1290–1 | date=May 2008 |pmid=18460535 |doi=10.1378/chest.07-2840 |url=}}</ref> 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.<ref>[http://www.ans.org/pubs/magazines/nn/docs/2000-1-3.pdf Air crew radiation exposure—An overview], Susan Bailey, Nuclear News (a publication of [[American Nuclear Society]]), January 2000.</ref>
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| == Cost per scan ==
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| As of August 2008, [[Cancer Care Ontario]] reports that the current average cost to perform a PET scan in the province is $1,000-$1,200 per scan. This includes
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| the cost of the radiopharmaceutical and a stipend for the physician reading the scan.<ref>{{Citation
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| == See also ==
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| * [[Diffuse optical imaging]]
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| * [[Hot cell]] (Equipment used to produce the radiopharmaceuticals used in PET)
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| * [[Molecular Imaging]]
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| ==References==
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| {{Reflist|2}}
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| == External links ==
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| {{Commons category}}
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| * [http://rad.usuhs.edu/medpix/master.php3?mode=image_finder&action=search&srchstr=&srch_type=all&labels=&details=2&no_filter=2&plane_id=&capt_id=-4&filter_m=modality&filter_o=&acr_pre=&filter_p=&acr_post=#top PET Images] Search MedPix(r)
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| * [http://www.natureprotocols.com/2006/12/21/seeing_is_believing_in_vivo_fu_1.php 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).
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| * [http://nuccast.com The nuclear medicine and molecular medicine podcast]—Podcast
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| * [http://www.np.ph.bham.ac.uk/pic/pept.htm 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.
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| * [http://www.hematologytimes.com/ht/p_article.do?id=948 CMS coverage of PET scans]
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| * [http://www.med.harvard.edu/JPNM/chetan/ PET-CT atlas Harvard Medical School]
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| * [http://isotopes.gov/ National Isotope Development Center]—U.S. government source of radionuclides including those for PET—production, research, development, distribution, and information
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| [[Category:3d nuclear medical imaging]]
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