Abstract WP96: Axonal Integrity of Normal Appearing White Matter Predicts Increased Burden of Leukoaraiosis

Abstract

Background: White Matter Hyperintensities (WMH) are thought to represent end-stage white matter injury. Increasing WMH burden is associated with greater risk of stroke, infarct growth, and poor outcomes after stroke. Understanding the microstructural changes of normal appearing white matter (NAWM) that predate WMH development is therefore clinically relevant as it could identify targets for therapeutic intervention to reduce stroke risk and improve post-stroke outcomes. Diffusion tensor imaging-based axial (AD) and radial diffusivity (RD) can assess white matter axonal integrity and myelin status, respectively. In a cohort of patients with acute ischemic stroke (AIS), we measured NAWM and WMH AD and RD to elucidate the white matter microstructural changes associated with WMH burden. Methods: Brain MRI with diffusion tensor imaging sequences was acquired within 48 hours of admission on consecutive AIS patients. WMH volume (WMHv) was measured in a semi-automated manner. Median fractional anisotropy, mean diffusivity, RD, and AD values were calculated within NAWM and WMH in the hemisphere contralateral to the acute lesion. Linear regression analysis was performed to evaluate predictors of WMH. Level of significance was set at P < 0.05 for all analyses. Results: In 319 AIS patients, mean age was 67 +/- 15.9 years. Median WMHv was 6.19 cm3 (IQR 3.0-12.6 cm 3 ). Mean AD was significantly increased in WMH compared to NAWM (WMH: 1.29 vs. NAWM: 1.16 x 10 -3 , mm 2 /s; P < 0.0001). In multivariable linear regression, age (β = 0.18, P = 0.017) and NAWM AD (β = 42.3, P = 0.012) were independent predictors of WMHv. Diffusivity anisotropy metrics of WMH were not associated with WMHv. Conclusions: In patients with AIS, NAWM AD is an independent predictor of WMHv. Our findings suggest that loss of NAWM axonal integrity contributes to WMH development.