Hyperosmolar blood-brain barrier disruption in baboons: An in vivo study using positron emission tomography and rubidium-82
Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8-to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 +/-2.4 microliter/min/ml (+/- standard deviation) at baseline and increased more than 100% (delta K1=9.4 +/-5.1 microliter/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p< 0.005). Vascular permeability returned to baseline with a halftime of 24.0 +/- 14.3 minutes. The mean brain plasma volume rose by 0.57 +/- 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.