Normal-Appearing White Matter Microstructural Injury Is Associated With White Matter Hyperintensity Burden In Acute Ischemic Stroke

Background White matter hyperintensity of presumed vascular origin is a risk factor for poor stroke outcomes. In patients with acute ischemic stroke, however, the in vivo mechanisms of white matter microstructural injury are less clear. Aims To characterize the directional diffusivity components in normal-appearing white matter and white matter hyperintensity in acute ischemic stroke patients. Methods A retrospective analysis was performed on a cohort of patients with acute ischemic stroke and brain magnetic resonance imaging with diffusion tensor imaging sequences acquired within 48 h of admission. White matter hyperintensity volume was measured in a semi-automated manner. Median fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter and white matter hyperintensity in the hemisphere contralateral to the acute infarct. Linear regression analysis was performed to evaluate predictors of white matter hyperintensity volume and normal-appearing white matter diffusivity metrics. Results In 319 patients, mean age was 64.9 +/- 15.9 years. White matter hyperintensity volume was 6.33 cm(3) (interquartile range 3.0-12.6 cm(3)). Axial and radial diffusivity were significantly increased in white matter hyperintensity compared to normal-appearing white matter. In multivariable linear regression, age (beta = 0.20, P = 0.003) and normal-appearing white matter axial diffusivity (beta = 37.9, P < 0.001) were independently associated with white matter hyperintensity volume. Subsequent analysis demonstrated that increasing age (beta = 0.004, P < 0.001) and admission diastolic blood pressure (beta = 0.001, P = 0.02) were independent predictors of normal-appearing white matter axial diffusivity in multivariable linear regression. Conclusions Normal-appearing white matter axial diffusivity increases with age and is an independent predictor of white matter hyperintensity volume in acute ischemic stroke.