Use of O-15 water and C-11 butanol to measure cerebral blood flow (CBF) and water permeability with positron emission tomography (PET)

Tracers used to measure CBF with PET and the Kety autoradiographic approach should freely cross the blood-brain barrier. 0-15 water, which is not freely permeable, may underestimate CBF, especially at higher flows. The authors determined this under-estimation relative to flow measured with a freely diffusible tracer, C-11 butanol and used these data to calculate the extraction (E) and permeability surface area product (PS) for 0-15 water. Paired flow measurements were made with 0-15 water (CBF-wat) and C-11 butanol (CBF-but) in eight normal human subjects. Average CBF-but, 55.6 ml/(min . 100g) was significantly greater than CBF-water, 47.6 ml/(min . 100g). The ratio of regional gray matter (GM) flow to white matter (WM) flow was significantly greater with C-11 butanol, indicating a greater underestimation of CBF with 0-15 water in the higher flow GM. Average E for water was 0.92 in WM and 0.82 in GM. The mean PS in GM, 148 ml/(min . 100g), was significantly greater than in WM, 94 ml/(min . 100g). Simulation studies demonstrated that a measurement error in CBF-wat or CBF-but causes an approximately equivalent error in E but a considerably larger error in PS due to the sensitivity of the equation, PS=-CBF . ln(1-E), to variations in E. Modest errors in E and PS result from tissue heterogeneity that occurs due to the limited spatial resolution of PET. The authors' measurements of E and PS for water are similar to data obtained by more invasive methods and demonstrate the ability of PET to measure brain water permeability