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

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 H₂¹⁵O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H₂¹⁵O, may lead to an underestimation of CBF. We therefore validated the use of [¹¹C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H₂¹⁵O, and thereby were able to calculate the extraction E_w and permeability–surface area product PS_w of H₂¹⁵O. Measurements of the permeability of rhesus monkey brain to [¹¹C]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 [¹¹C]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 H₂¹⁵O and [¹¹C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [¹¹C]butanol (53.1 ml/min-100 g) than with H₂¹⁵O (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 [¹¹C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PS_w.