Introduction

The importance of blood–brain barrier (BBB) integrity has long been recognized and BBB permeability has been measured using invasive tracer techniques in experimental animals. Since the development of positron emission tomography (PET), non-invasive measurement of BBB permeability in humans has become feasible. Although the integrity of the BBB in man has also been examined using contrast CT, MRI, and radioscintigraphy, the results are mostly qualitative, i.e. they do not provide the permeability–surface area product (referred to simply as permeability in this chapter) in terms of ml/min/g. Without a quantitative measure, BBB changes due to disease progression, treatment, and pharmacological interventions cannot be easily assessed. PET has been successfully employed to examine BBB permeability in man in various diseases and pharmacological interventions (Brooks et al., 1984; Hawkins et al., 1984; Lockwood et al., 1984; Iannotti et al., 1987; Schlageter et al., 1987; Pozzilli et al., 1988; Ott et al., 1991; Black et al., 1997). In the following, the basic principles used in these techniques are introduced and the procedure, requirements, and typical results are reviewed.

Basic principles

For a systemically administered tracer to get to the extra-vascular space of the brain tissue, the tracer needs to be delivered first to the capillaries in the brain tissue by cerebral blood flow (or perfusion) (CBF) and then transported across the BBB.