Background and Purpose: Contrast-enhanced magnetic resonance imaging (CE-MRI) is used to measure blood-brain barrier (BBB) damage after stroke, but is contra-indicated in patients with compromised kidney function. Thus, there is a need for non-contrast MRI techniques that portend BBB damage. We examined the relationships between CE-MRI and non-contrast MRI measures to test whether the latter serve as surrogate biomarkers of BBB damage in acute stroke.
Methods: Male Wistar rats (∼300 g; N=22) were subjected to focal cerebral ischemia-reperfusion using a middle cerebral artery suture occlusion model. They were imaged in a 7 Tesla Bruker MRI system. The parameters measured were: cerebral blood flow (CBF), T2, T1 and T1-under-off resonance-saturation (T1sat). All data except CBF were expressed as ipsilateral-to-contralateral ratios (I-C). Post-reperfusion BBB damage was measured by CE-MRI via blood-to-brain forward volumetric transfer constant (Ktrans) maps. CBF, T2, T1 and T1sat were compared to Ktrans from the same region of interest (ROI). Scatterplots with Pearson correlation coefficients (r) were used to compare the data and significances inferred at p<0.05.
Results: Preoptic area (PoA) and striatum (Str) were found ischemic in nearly all rats, with neocortical areas lesser affected. During occlusion, CBF in PoA and Str were 26±15 and 42±18 ml/100g/min (20-25% of contralateral side), respectively. After reperfusion, CBF was 78±27 and 99±50 ml/100g/min in PoA and Str, respectively. Contrast enhancement or BBB damage was observed in the PoA in all 22 rats and in 17 in Str. The I-C values of T2, T1 and T1sat elevated between occlusion and reperfusion periods and were associated with increased Ktrans values (p=0.05). The extent of CBF reduction during occlusion was significant and correlated inversely with increased Ktrans (r=-0.5; p=0.03), but this relationship was lost after reperfusion (r=0.3; p=0.3).
Conclusions: The data suggest that reduction in CBF during occlusion and post-reperfusion elevation of T2, T1, and T1sat (i.e. vasogenic edema) are reliable predictors of impending BBB damage in acute stroke. With further confirmation, non-contrast based MRI evaluation of the BBB in acute stroke may be utilized in cases where CE-MRI is not possible.