Introduction

The terms indicator diffusion, double-indicator, single injection or indicator dilution have been used interchangeably for this technique, the principles of which were outlined by Chinard et al (1955) and first applied in the brain by Crone, who also provided the first quantitative measurements of capillary permeability and demonstrated a carrier-mediated transport of D-glucose across the Blood–brain barrier (BBB) (Crone, 1965). In 1971, the method was applied in humans by Lassen and co-authors, and later used in several clinical studies (Bolwig et al., 1977; Paulson et al., 1977; Hertz and Paulson, 1980, 1982; Knudsen et al., 1990a,b 1991, 1995; Hasselbalch et al., 1995, 1996). In 1994, the intravenous indicator diffusion method was developed (Knudsen et al.). A more detailed description of its application in humans has been given previously (Knudsen, 1994b).

The indicator diffusion technique for BBB permeability measurements has classically been applied as follows (Fig. 14.1): An intracarotid bolus injection of isotopically labeled test and BBB impermeable reference substance is given, immediately followed by a rapid series of blood sampling from the internal jugular vein in humans or from the sagittal sinus in rats. If closely matching tracer substances have been chosen and the venous concentration of each tracer is normalized with the injectate concentration then the time course of the brain outflow curves of the test and reference substances are known.