Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [15O]Water and [11C]Butanol

Abstract

We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H 215 O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H 215 O, may lead to an underestimation of CBF. We therefore validated the use of [11 C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H 215 O, and thereby were able to calculate the extraction E w and permeability–surface area product PS w of H 215 O. Measurements of the permeability of rhesus monkey brain to [11 C]butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and [11 C]butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H 215 O and [11 C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [11 C]butanol (53.1 ml/min-100 g) than with H 215 O (44.4 ml/min-100 g). Average global E w was 0.84 and global PS w was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PS w and CBF, while E w was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain–blood partition coefficient for [11 C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PS w.