A dual label radiotracer technique for the simultaneous measurement of cerebral blood flow and the single-transit cerebral extraction of diffusion-limited compounds in rats

An inexpensive method is described which permits simultaneous quantification of the cerebrovascular extraction (E) of diffusion-limited compounds and cerebral blood flow (CBF) in rats. This method involves the use of two radioisotopic tracers: (a) a diffusion-limited, test tracer such as [³H]water; and (b) a reference tracer. The reference tracer is also used in the measurement of CBF. In the development and validation of this technique, results using two different types of reference tracers were compared. The reference tracers empoyed were: (a) [¹⁴C]butanol, a flow-limited (i.e. freely diffusible) compound; and (b) [¹⁴¹Ce]microspheres which embolize in the cerebromicrocirculation. Inclusion of [³H]water in the injection bolus permitted simultaneous measurement of E_w using both butanol and microspheres as the reference as well as concomitant measurement of CBF. Both tracers provided estimates of these values which behaved physiologically with respect to increasing arterial CO₂ content (p_aCO₂). In addition, the simultaneous measurement of E_w and CBF permitted calculation of the effective permeability of water across the blood-brain barrier (P_wS) which was discovered to increased with increasing p_aCO₂.