There are a number of limitations associated with PET. First, it must be remembered that one is simply measuring emitted radioactivity. Thus, in order for a measure to be biologically meaningful, one must have some theoretical and/or experimental basis for understanding what the radioactivity represents-for example, conversion to a metabolite that is trapped (specific binding), as well as some measure of the radioactivity input function (nonspecific uptake/binding, etc.). Secondly, although PET excels in the measurement of certain types of function, its spatial resolution is limited compared with MRI and even CT. Even the best current scanners for human use have a resolution of 2-3 mm, and 5-10 mm is more usual (and worse following reconstruction). This leads to difficulty distinguishing between smaller regions of interest, difficulty quantifying activity in small regions, and greater susceptibility to partial volume effects than is seen with structural imaging techniques. The partial volume problem is compounded by the fact that one is not simply looking at the contrast between preserved structure and loss of structure, but rather between areas of high and low function. The temporal resolution of PET is also limited, in part, by the time required to detect adequate signal. During this time, dynamic changes may be taking place in the biological process under study. The long time required for most PET studies is also a challenge for patients, who may find it difficult to lie still in the scanner, and the measures may be degraded by head motion. Finally, although the risk is thought to be extremely small, PET depends upon the injection of radioactively tagged molecules. By definition, the dose of the molecule itself should be small enough to have no pharmacological (or adverse) effect; however, radiation dosimetry may be an issue, particularly if performing repeated studies with multiple tracers in younger individuals.
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