Abstract
Variations in apparent diffusion coefficient of water (ADC) and blood-brain barrier (BBB) permeability after ischemia have been suggested, though the correlation between ADC alterations and BBB opening remains to be studied. We hypothesized that there are correlations between the alteration of ADC and BBB permeability. Rats were subjected to 2 h of transient middle cerebral artery occlusion and studied at 3 and 48 h of reperfusion, which are crucial times of BBB opening. BBB permeability and ADC values were measured by dynamic contrast-enhanced MRI and diffusion-weighted imaging, respectively. Temporal and spatial analyses of the evolution of BBB permeability and ADC alteration in cortical and subcortical regions were conducted along with the correlation between ADC and BBB permeability data. We found significant increases in BBB leakage and reduction in ADC values between 3 and 48 h of reperfusion. We identified three MR tissue signature models: high Ki and low ADC, high Ki and normal ADC, and normal Ki and low ADC. Over time, areas with normal Ki and low ADC transformed into areas with high Ki. We observed a pattern of lesion evolution where the extent of initial ischemic injury reflected by ADC abnormalities determines vascular integrity. Our results suggest that regions with vasogenic edema alone are not likely to develop low ADC by 48 h and may undergo recovery.
Highlights
The use of magnetic resonance imaging (MRI) techniques, including apparent diffusion coefficient (ADC) obtained by diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and contrast-enhanced MRI has been increasingly important in evaluating various treatment strategies in both experimental models of cerebral ischemia [1,2,3,4] and stroke patients [5,6,7,8,9,10]
Marked regional differences were observed in the degree of increment in Blood-brain barrier (BBB) permeability and reduction in ADC values in cerebral cortex and subcortical regions at 3 and 48 h following 2 h of middle cerebral artery occlusion (MCAO)
The extent of the lesion calculated based on the altered ADC and BBB permeability was larger at 48 h compared with 3 h in cerebral cortex and subcortical areas
Summary
The use of magnetic resonance imaging (MRI) techniques, including apparent diffusion coefficient (ADC) obtained by diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and contrast-enhanced MRI has been increasingly important in evaluating various treatment strategies in both experimental models of cerebral ischemia [1,2,3,4] and stroke patients [5,6,7,8,9,10]. Using either the 14C-Sucrose quantitative method or the extravasation of Evans blue-albumin, others and we had previously described a biphasic opening of the BBB in the rat middle cerebral artery occlusion (MCAO) stroke model [11,12,13]. There is an early significant increase in BBB opening after 2–3 h of reperfusion following MCAO, the timing of which depends on the duration of ischemia [14]. After this initial opening, the BBB restores its functions and no significant changes in permeability to either 14C-sucrose or Evans blue-albumin are observed until 24 to 48 h after reperfusion.
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