Our understanding of the pathophysiology of Parkinson's disease (PD) has been based largely on studies of postmortem brain tissue, and on observations of animal models. Although x-ray computed tomography and magnetic resonance (MR) imaging have made it possible to correlate in vivo anatomical abnormalities with disease processes, these structural neuroimaging techniques have thus far contributed little to our knowledge of PD, for which the changes within the brain relate more to neurochemistry and function than to structure. With the development of positron emission tomography (PET) has come the ability to study cerebral function, on a regional basis, with anatomical resolution sufficient to separate major subcortical structures such as the thalamus, caudate, and putamen.
PET is a quantitative imaging technique that permits regional measurement of radioactivity after the administration of positron-emitting isotopes. By using appropriately labeled compounds, a tomographic section corresponding to an image of regional radioactivity in the brain may be reconstructed. The distribution of radioactivity depends on the tracer compound administered and on local cerebral physiological and biochemical processes, which may then be quantified by applying the principles of tracer kinetic analysis. Quantifiable processes that have been studied by PET include regional cerebral blood flow (rCBF) and blood volume, and metabolism of oxygen (rCMRO,) and glucose (rCMRG). The major energyconsuming process in the brain is that of the ion transport mechanisms that maintain the electrochemical gradients necessary for the generation of action potentials. The mapping of rCMRO, or rCMRG with PET, therefore, provides an image of functional (i.e., energy-consuming) brain activity. Because rCBF is thought to be closely coupled to tissue metabolic demands, mapping of rCBF provides a similar image of brain function. In addition, it is now possible to assess abnormalities of both presynaptic and postsynaptic neurotransmitter function, although the tracer kinetic modeling process is less complete for these measurements than for the quantitation of blood flow and metabolism.
CEREBRAL METABOLISM AND BLOOD FLOW
In animals with unilateral nigrostriatal lesions, metabolism is increased in the ipsilateral globus pallidus. This increase has been suggested to reflect increased