Study of cerebral function with positron computed tomography

Abstract

Positron computed tomography (PCT) is a technique that permits both the tomographic delineation of cerebral structures and the measurement of the local tissue concentrations of injected radioactive tracers. The latter provides a means of implementing quantitative tracer kinetic techniques for the measurement of functional processes in the human brain. This is analogous to measurements in animals of local tissue radioactivity concentrations with autoradiography or by excision of tissue samples. However, with PCT, this measurement is performed noninvasively using external radiation detection and mathematical image reconstruction techniques. Some of the labeled compounds used in PCT are analogous to those commonly used in animal studies. For example, carbon-14, which is not detectable externally, is substituted with the positron emitting isotrope carbon-11. There is no positron emitting isotope of hydrogen, but fluorine-18 is used as a substitute for hydrogen because its strong carbon-fluorine bond (109 kcal) and because its similar size produces minimal changes in steric hindrance. However, its difference in electronegativity can produce effects different from those produced by hydrogen. The use of nitrogen-13 and oxygen-15 is unique to PCT. Thus, the positron-emitting isotopes of carbon, nitrogen, oxygen, and fluorine can be used to label a wide variety of substrates, metabolites, drugs and other biologically active compounds or their analogs without disrupting their chemical or biochemical properties. Together with the quantitative measurement properties of PCT and tracer kinetic models, this provides unique ways of measuring local biochemical processes in the human brain. PCT requires effective integration of a number of technologies to provide estimates of local physiological or biochemical processes. First, the tomography must be capable of performing analytical measurements of local tissue radioactivity concentrations noninvasively in man. Second, labeled compounds that trace a physiological process in a known and predictable manner are required. Third, tracer kinetic models must be used that describe the process under study and allow the calculation of the rate of the process within the limitations of the type of data provided by PCT. Each of these areas will be discussed in this paper with specific examples. Since the technique provides more than tomographic images, it has been referred to as physiological tomography (PT) to denote the specific type of information provided (Phelps et al., 1977a). Due to the relatively early stage of development of PT, applications will be primarily limited to those areas in which the number of investigations performed is sufficient to provide reasonable prospectives or to illustrate unique features of the method.