Abstract WP43: Advanced White Matter Disease is Associated With Increased Blood-Brain Barrier Permeability and Early Diffuse Microstructural Changes in Patients With Acute Ischemic Stroke

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Background: In acute ischemic stroke (AIS), cerebral tissue damage and clinical outcomes are linked to pre-existing microvascular dysfunction, manifesting as white matter hyperintensity (WMH). Elevated blood-brain barrier permeability (BBB-P) has been implicated in advanced WMH. We tested the microstructural integrity of BBB as measured by dynamic susceptibility contrast (DSC) MRI K2 coefficient values in AIS patients with advanced WMH.

Methods: Twenty patients enrolled in a prospective acute MRI study underwent diffusion tensor (DTI) and DSC MRI on admission for AIS. BBB-P estimates were derived from DSC MRI using the K2 coefficients. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) maps were calculated. Mean K2, MD, AD, RD and FA values were measured in regions of WMH and normally appearing white matter (NAWM) in the hemisphere contralateral to AIS and compared (two-tailed Student t-Test). WMH volume (WMHv) was assessed on acute FLAIR using a validated semi-automated volumetric protocol. Linear regression was performed to evaluate significant predictors of K2, MD, AD, RD, and FA. Correlation analysis was performed (Pearson product-moment).

Results: Mean age of subjects was 66 (±10) years, 30% were women, median WMHv 3.5cm3 [IQR 1.6-7.4]. K2 values differed significantly between WMH and NAWM (0.32 x10-3 vs. 1.1 x10-3, p<0.03), as did the diffusivity metrics for WMH and NAWM (FA: 0.25 vs 0.38; MD: 1.3 x10-3vs 0.84 x10-3; AD: 1.6 x10-3vs 1.2 x10-3; RD: 1.14 x10-3vs 0.66 x10-3; all p<0.0001). K2and RDvalues were correlated within WMH (R=-0.45, P=0.046) but not in NAWM (R=0.06, P=0.81). Multivariate analysis found systolic BP (SBP) and lnWMHv to be significant predictors of MD (P=0.0009), AD (P=0.002), and RD (P=0.002) in NAWM.

Discussion: BBB-P and diffusivity values in patients with AIS and advanced leukoaraiosis differed significantly between WMH and NAWM in the hemisphere contralateral to acute infarct. Association between the RD and K2coefficients in WMH suggests the role of BBB-P in pathophysiology of WMH and the loss of microstructural white matter integrity associated with it. Further, the influence of SBP and lnWMHv on NAWM diffusivity values suggests ongoing risk for developing future WMH.

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