Single photon emission computed tomography, SPECT, allows the measurement of the 3-d distribution of radioactive tracers in brain. Tracers in use fall into two main classes. In the first class, the tracer is taken up in brain in proportion to blood flow and thus can be utilized as a marker of neural activity. The second class of tracers binds to sites in brain such that the activity then reflects the distribution of the related neurochemistry. Previous work focused on the use of Xenon-133 and Xenon-127 for absolute flow measurements during cognitive activation tasks. Newly available perfusion related tracers using Tc 99m labeled tracers have been studied to determine their ability for rCBF measurements using dose normalization and split dose activation paradigms. Neurochemistry studies have involved IQNB, a muscarinic receptor antagonist, and IBZM, a D2 dopamine receptor antagonist. SPECT IQNB scans demonstrated focal areas of reduced uptake in patients with dementia. Current studies involve using IQNB to determine if receptor up-regulation is possible in a clinical population. IBZM scans are processed into time activity curves allowing the determination of specific binding kinetics. Kinetic parameters in patients with asymmetrical Parkinson's disease and with Tourette's Syndrome appear to provide a sensitive measure of clinically meaningful dopamine function. Studies in schizophrenic patients treated with clozapine have shown a curvilinear relation between blood level and estimated D2 receptor occupancy. Modeling studies have developed graphical analysis techniques that allow quantitative determination of multicompartment kinetic parameters. Studies to examine patients with schizophrenia at different points during a drug washout phase are underway. Such studies will allow examination of the presumed hyerdopaminergic state in these patients.
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