ANALYSIS OF DYNAMIC RADIOLIGAND DISPLACEMENT OR ACTIVATION STUDIES

We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission t omography (PET) activation studies. The approach is designed to facili tate dynamic activation studies using selective radioligands. These st udies are, in principle, capable of characterising functional neuroche mistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent com partmental models of tracer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive, voxel-based and data-led assessment of regionally specific effects. T he statistical model proposed in this paper is predicated on a single- compartment model extended to allow for time-dependent changes in kine tics. We have addressed the sensitivity and specificity of the analysi s, as it would be used operationally, by applying the analysis to C-11 -Flumazenil dynamic displacement studies. The activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge, 30 min after administration of the tracer. We were able to demonstrate , and make statistical inferences about, regional increases in k(2) (o r decreases in the volume of distribution) in prefrontal and other cor tical areas.