Positron Emission Tomography

PET was developed from in vivo autoradiographic techniques. In an autoradiographic procedure, an animal is typically injected with a biologically interesting compound synthesized with a radioisotope (e.g., 3H). When the animal is sacrificed, the local tissue radioactivity is easily quantified. Although autoradiography yields exquisitely detailed pictures of brain activity, it can only be applied in animals, and the animals must be sacrificed to obtain the brain tissue. Although these techniques were in use in the 1950s and 1960s, the development of an in vivo method applicable to humans awaited technological advancements from the "silicon revolution"—namely, the availability of high-quality inexpensive crystal detectors and the huge advancements in computing power realized in the late 1970s.

PET requires three basic technologies: the production of positron-emitting compounds, the ability to detect simultaneously emitted gamma rays, and the computational power to reconstruct the sources of emission. Positrons, or positively charged electrons (antimatter), have a particular advantage over other radioactive compounds. When a positron encounters an electron, the two annihilate each other, and their collective energy is transformed into two high-energy photons that are emitted in exactly opposite directions. Because the photons travel 180° apart, it is easy to arrange a ring of detectors to determine where the annihilation occurred. When two detectors are activated simultaneously, then one knows that the emission occurred somewhere along the line connecting the two detectors. By collecting the counts over a period of time, say 60 seconds, and over a full sphere surrounding the subject's head, it becomes possible to reconstruct the geometry of the source.

Positrons are produced indirectly, through the radioactive decay of particular isotopes. The most

11 15 18 13

commonly used isotopes (carbon-11 [ C], oxygen-15 [ O], fluorine-18 [ F], nitrogen-13 [ N]) are produced in a cyclotron by the bombardment of targets with high-energy protons. This results in a gas (e.g., 15O2), which can then be used in any chemical reaction (e.g., oxidation-reduction reaction with product H215O). After appropriate purification procedures, these compounds can then be injected intravenously into a human subject, and they flow to the brain in about 20 seconds. The isotope undergoes radioactive decay by positron emission, and the half-life depends on the particular isotope (e.g., 2 minutes for 15O).

Because the photons emitted during positron decay are fairly high in energy (511-keV gamma rays), they tend to pass through matter with relative ease. A specialized detector, called a scintillation detector, is required to accurately count the decays in a directional fashion. PET scanners consist of rings of these detectors arranged in parallel planes. An individual detector would be constructed from a scintillating crystal, either bismuth germanate (BGO) or lutetium oxyorthosilicate (LSO), and amplification electronics. When a gamma ray enters the crystal, it loses its energy through either the photoelectric or Compton effect, which results in the production of electrons. These electrons further interact with the crystal, resulting in the production of visible wavelength photons. These photons are then detected and amplified by a photomultiplier tube and converted into an electrical pulse. A "coincidence circuit" allows for the identification of the detector that picks up the 180°-emitted gamma ray.

Depending on the injected molecule, a particular regional distribution will occur. In the case of H215O, it will follow the rCBF. Other compounds will cross the blood-brain barrier and bind to specific receptors, in which case the distribution of radioactivity will reflect receptor concentration. Fluorodeoxyglucose-18

(18FDG), a commonly used tracer, is metabolized by hexokinase during glycolysis, like glucose. Unlike

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