Post-ischemic leakiness of the blood–brain barrier: A quantitative and systematic assessment by Patlak plots

Abstract

The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood–brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant ( K i) of the contrast agent gadolinium, distribution volume ( V p), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, K i, measured at all time-points, except for 5 weeks, appeared significantly different ( p < 0.001). At several time-points (25 min, 48 and 72 h, 4 and 5 weeks), V p was similar compared to that of controls, but for the remaining groups the difference was significant ( p < 0.001). Analyzing the relationship of K i values to time-points, we observed a trend towards a decrease over time ( r = − 0.61, p = 0.014). Both ADC values ( r = − 0.58, p = 0.02) and ischemic lesion volumes ( r = 0.75, p = 0.0015) correlated with K i values. These results suggest that after ischemia–reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury.