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 radio-Xenon for absolute flow measurements during cognitive activation tasks. This work was extended to perfusion related tracers using Tc-99m to determine their ability for rCBF measurements using dose normalization and split dose activation paradigms. While this work was largely successful, other more sensitive means exist for CBF measurements leaving us to concentrate on the use of SPECT for neurochemistry. Our main area of interest is the dopamine system where we are able to examine postsynaptic receptor density using IBZM and to also measure the presynaptic side with beta-CIT, a marker for the dopamine reuptake transporter. IBZM studies in normal volunteers, Parkinson's Disease patients with clinical asymmetrical presentation, and identical twins with Tourette's syndrome have established that this technique is able to provide a sensitive measure of clinically meaningful dopamine function. Studies in schizophrenic patients, both drug free and treated with various neuroleptics have shown a curvilinear relation between blood level and estimated D2 receptor occupancy as well as showing a relation between dopaminergic measures and clinical symptomatology. Other neurochemistry studies involve IQNB, a muscarinic 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. We have compared normal controls with Alzheimer patients on both perfusion scans and IQNB after chronic low dose scopolamine. The difference in groups was marked when comparing the ratio I-QNB to HMPAO uptake, indicating a double dissociation and suggesting a differential sensitivity to chronic cholinergic blockade.
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