Abstract TP259: Surrogate MRI Signatures for Contrast Enhanced Imaging That Predict Acute Blood-brain Barrier Damage in Ischemia-reperfusion

Abstract

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), T 2 , T 1 and T 1 -under-off resonance-saturation (T 1sat ). 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 (K trans ) maps. CBF, T 2 , T 1 and T 1sat were compared to K trans 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 T 2 , T 1 and T 1sat elevated between occlusion and reperfusion periods and were associated with increased K trans values ( p =0.05). The extent of CBF reduction during occlusion was significant and correlated inversely with increased K trans (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 T 2 , T 1 , and T 1sat (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.