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.