Abstract
Mechanisms that underlie early ischemic damages to the bloodโbrainโbarrier (BBB) are not well understood. This study presents a novel magnetic resonance imaging (MRI) technique using a widely available pulse sequence and a longโcirculating 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 exchangeโaffected 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 intraโ/extravascular WEI for 4 hours. Statistically significant elevations (P < 0.05) of WEI in the ischemic tissue were observed as early as 1 hour after ischemic onset. Initial reduction of the apparent blood volume (V~app~) in the infarct cortex was followed by a continuous increase of V~app~ over time. Although the measured ADC in the ipsilesional cortex continuously decreased, the abnormally high intraโ/extravascular WEI remained constant at a significantly elevated level, indicating apparent BBB injury at this early stage of stroke. Magn Reson Med 60:813โ821, 2008. ยฉ 2008 WileyโLiss, Inc.