Imaging Techniques Visualizing

THE LIVING BRAIN Images of the human BRAIN constructed using sophisticated computer systems have proven valuable for studying the effects of abused drugs. Nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), allow noninvasive studies of brain function in human volunteers by the administration of small amounts of radioisotopes. These procedures allow visualization and quantification of biochemical processes in the living brain. Functional MRI (magnetic resonance imaging) is a recently developed technique that makes it possible to construct functional brain images without radiation.

PET scanning uses radioisotopes that decay by emitting positrons (positively charged particles), which collide with electrons (negatively charged particles that surround atomic nuclei). In each collision, both the electron and positron are annihilated and energy is released in the form of two photons (quanta of light) that move in opposite directions. The detectors of a PET scanner surround the tissue being studied and register the arrival of photons. The associated computer system can calculate the location of each collision and reconstruct an image of the concentration of radioactivity in different parts of the tissue.

The most common applications of PET scanning involve functional measurements of cerebral (brain) metabolism or cerebral blood flow. PET is also used to map and quantify specific RECEPTORS for drugs and NEUROTRANSMITTERS in the brain. Cerebral glucose consumption (metabolism) and cerebral blood flow both reflect the activity of brain cells. Under normal circumstances, the cerebral metabolism and blood flow are tightly coupled. The most active brain cells require the most glucose, a sugar that is the primary energy source of the adult brain. Brain regions that contain the active cells also require high rates of blood flow for the delivery of nutrients and oxygen. In some conditions, however—including those caused by some drugs— cerebral metabolism and blood flow rates may be dissociated.

Rates of consumption of glucose in the whole brain or in specific brain regions have been measured using fluorodeoxyglucose (FDG) labeled with the positron-emitting isotope fluorine-18 (18F). Cerebral blood flow has been measured using oxy gen-15 (15O), either inhaled in C15O2 or injected in 15O-labeled water.

In SPECT, radionuclides that emit single photons are used, including iodine-123 (123I) and technetium-99m (99mTc), and the photons are measured using a rotating gamma camera. The isotopes used in SPECT have longer half-lives (thirteen hours for 123I and six hours for 99mTc than those used in PET (110 minutes for 18F and 10 minutes for 15O). Therefore, whereas PET generally requires an on-site cyclotron to produce radioisotopes, SPECT radioactive tracers can be made elsewhere and brought in for use. Although SPECT produces useful images, it does not provide either the quantitative precision or the spatial resolution of PET. Currently available PET scanners can resolve differences in the radioactivity of objects only 4 to 5 millimeters (mm) apart, while the resolution of new SPECT scanners is for 6 to 8 mm.

Before the advent of PET and SPECT, blood flow was measured using xenon-133, given by brief inhalation or intracarotid artery injection. Xenon-133 has a gamma emission with a half-life of 5.27 days, and the radioactivity is monitored outside the skull by an array of detectors that each record a beam of particles from a specific location. Unlike PET, the xenon-133 methods do not provide tomographic information—they do not produce images of ''slices'' of the brain. Therefore, activity in deep brain structures cannot be measured this way.

Recent advances in magnetic resonance imaging (MRI) technology have permitted functional measurement of cerebral blood volume, which is closely related to cerebral blood flow. Functional MRI assessments are based upon the difference between the paramagnetic properties of oxygenated and unoxygenated hemoglobin. Activation of a brain area causes increased blood flow to the region. Oxygen carried to the activated region is delivered in excess of that which is required by the increased activity. Therefore, it accumulates, as does oxyhe-moglobin. Functional MRI produces brain images of very spatial and temporal resolution.

Since researchers are interested in the activity of specific brain structures, data are obtained by functional imaging techniques often adjusted (normalized) to remove the effects of differences between individuals in whole brain activity measurements considered irrelevant to the question under study. Normalized data may be expressed numerically as the quotient of the activity in a region of interest divided by the activity in the whole brain or in the slice containing the region. Such data are not always easy to interpret, since changes in the denominator can obscure the direction and magnitude of change in a region.

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