LAUSR

Background: Early outcome prediction after acute ischemic stroke (AIS) is critical to guide care and rehabilitation strategies. Pre-existing chronic structural injury to cerebral white matter (WM), including ischemic WM hyperintensity (WMH) and microstructural changes within the normal-appearing WM (NAWM), is known to impede post-stroke recovery. Quantitative assessment of total pre-existing WM injury may therefore improve prognostication of functional stroke outcomes. Peak width of skeletonized mean diffusivity (PSMD) is an automated marker of cerebral small vessel disease and global WM injury. In a cohort of AIS patients, we measured PSMD in the hemisphere contralateral to the acute infarct and characterized its association with 90-day functional outcomes. Methods: Brain MRI with diffusion tensor imaging sequences was acquired within 48 hours of AIS admission. WMH volume (WMHv) was measured in a semi-automated manner. NAWM masks were constructed by subtracting the WMH and chronic infarct masks from a probabilistic WM atlas. NAWM mean diffusivity (MD) was then measured in the NAWM mask. PSMD was extracted by skeletonizing the WM tracts in the MD image using the Fractional Anisotropy image and the FSL Tract-Based Spatial Statistics pipeline with a mask for the contralesional hemisphere. Excellent outcome was defined as a modified Rankin scale score < 2 at 3-6 months post-stroke. Logistic regression analysis was performed to evaluate predictors of excellent outcome. Results: In 292 AIS patients, increasing PSMD and NAWM MD, but not WMHv, were associated with decreased likelihood of excellent outcome in univariable analysis. Increasing age, admission NIHSS score, DWI volume, and female sex were also negatively associated with excellent outcome. In backward stepwise logistic regression, including all significant variables from the univariable step, increasing age (β = -0.03; P = 0.01), NIHSS (β = -0.1; P = 0.0005), DWI volume (β = -0.02; P = 0.0004), PSMD (β = -0.08; P = 0.03), and female sex (β = -0.7; P = 0.01) were associated with decreased likelihood of excellent outcome. Conclusion: In AIS patients, automated determination of contralesional PSMD, as a marker of chronic, global white matter injury, is an independent predictor of functional outcomes.