Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats

Abstract

Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K_w) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K_w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K_w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K_w. Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K_w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K_w showed substantial overlap with regions of hyperintense T₂ (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K_w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min^-1, respectively (P < 0.05, n = 9). K_w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K_w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

Keywords: Cerebral ischemia; Evans blue; arterial spin labeling; dynamic contrast-enhanced magnetic resonance imaging; hyperperfusion; perfusion imaging; rats; vasogenic edema.

Figure 1.

Experimental protocol of MCAO, reperfusion, MRI and EB measurement performed on rats.

Figure 2.

Typical ADC, CBF, A₂, DCE_subtraction and K^Trans maps at day 0 after stroke (n= 9). Reperfusion was performed at 60 min after MCAO. ADC and CBF at 30 min after stroke during occlusion are also shown for reference, along with ROI definition for normal (blue), mismatch (green) and core (red). Scale bar: ADC (0–0.0001 s/mm²), CBF (0–1.5 ml/g/min), A₂ (0.4–1.4), DCE_subtraction (0–25,000 signal unit), K^Trans (0–0.003 min⁻¹).

Figure 3.

Group average values for ADC, CBF, DCE_subtraction and A₂ in normal, mismatch and core tissue types at day 0. Error bars represent standard deviation around the mean values. ADC and CBF were acquired at 30 min after MCAO and 75 min after MCAO (after reperfusion). A₂ and DCE MRI were acquired at 90 min after MCAO, respectively.

Figure 4.

Typical T₂, ADC, CBF, T₁, A₂, DCE_subtraction, K^Trans maps and EB slices 2 days after stroke. The ROI definitions for normal (green) and infarcted tissue (red) are drawn on T₂ maps. Scale bar are: T₂ (40–120 ms), T₁ (1250–2500 ms), ADC (0–0.0001 s/mm²), CBF (0–1.5 ml/g/min), A₂ (0.4–1.4), DCE_subtraction (0–25,000 signal unit), K^Trans (0–0.003 min⁻¹).

Figure 5.

Group average values for T₂, ADC, CBF, T₁, A₂, DCE_subtraction and K^Trans for normal and infracted tissue 2 days after MCAO. Error bars represent standard deviation around the mean values.