Abstract

Mechanisms that underlie early ischemic damages to the blood-brain-barrier (BBB) are not well understood. This study presents a novel magnetic resonance imaging (MRI) technique using a widely available pulse sequence and a long-circulating intravascular contrast agent to quantify water movements across the BBB at early stages of stroke progression. We characterized the integrity of the BBB by measuring the flip angle dependence of the water exchange-affected MRI signal intensity, to generate an efficient quantitative index of vascular permeability (WEI, or water exchange index). We performed in vivo MRI experiments to measure the transvascular WEI immediately after the permanent filament occlusion of the middle cerebral artery of mice (n = 5), in which we monitored changes in blood volume (V(b)), apparent diffusion coefficient (ADC), and intra-/extravascular WEI for 4 hours. Statistically significant elevations (P