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 cm3 (interquartile range 3.0-12.6 cm3). Axial and radial diffusivity were significantly increased in white matter hyperintensity compared to normal-appearing white matter. In multivariable linear regression, age (β = 0.20, P = 0.003) and normal-appearing white matter axial diffusivity (β = 37.9, P < 0.001) were independently associated with white matter hyperintensity volume. Subsequent analysis demonstrated that increasing age (β = 0.004, P < 0.001) and admission diastolic blood pressure (β = 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.