Characterizing the Penumbras of White Matter Hyperintensities and Their Associations With Cognitive Function in Patients With Subcortical Vascular Mild Cognitive Impairment

Abstract

Normal-appearing white matter (NAWM) surrounding white matter hyperintensities (WMHs), frequently known as the WMH penumbra, is associated with subtle white matter injury and has a high risk for future conversion to WMHs. The goal of this study was to define WMH penumbras and to further explore whether the diffusion and perfusion parameters of these penumbras could better reflect cognitive function alterations than WMHs in subjects with subcortical vascular mild cognitive impairment (svMCI). Seventy-three svMCI subjects underwent neuropsychological assessments and 3T MRI scans, including diffusion tensor imaging (DTI) and arterial spin labeling (ASL). To determine the extent of cerebral blood flow (CBF) and DTI penumbras. A NAWM layer mask was generated for periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) separately. Mean values of CBF, fractional anisotropy (FA), mean diffusivity (MD) within the WMHs and their corresponding NAWM layer masks were computed and compared using paired t-tests. Pearson's partial correlations were used to assess the relations of the mean CBF, FA, and MD values within the corresponding penumbras with composite z-scores of global cognition and four cognitive domains controlling for age, sex, and education. For both PVWMHs and DWMHs, the CBF penumbras were wider than the DTI penumbras. Only the mean FA value of the PVWMH-FA penumbra was correlated with the composite z-scores of global cognition before correction (r = 0.268, p = 0.024), but that correlation did not survive after correcting the p-value for multiple comparisons. Our findings showed extensive white matter perfusion disturbances including white matter tissue, both with and without microstructural alterations. The imaging parameters investigated, however, did not correlate to cognition.

Keywords: cerebral blood flow; diffusion tensor imaging; normal appearing white matter; penumbra; subcortical vascular mild cognitive impairment; white matter hyperintensity.

Figure 1

The spatial relationship between PVWMH, DWMH, and their corresponding NAWM layer masks. The turquoise and yellow represent WM lesions and NAWM layers, respectively. The innermost layer surrounding the WMH represents layer 1, and the outermost layer represents layer 15. (A) periventricular white matter hyperintensity (PVWMH); (B) deep white matter hyperintensity (DWMH).

Figure 2

Group means of the PVWMH (the left column) and DWMH (the right column) and their outer NAWM layers. The solid horizontal and dotted lines represent the mean and standard error of the whole-brain NAWM CBF, FA, and MD values, respectively. Red arrows represent the outer boundary of WMH penumbra for each dataset. (A) PVWMH-CBF; (B) PVWMH-FA; (C) PVWMH-MD; (D) DWMH-CBF; (E) DWMH-FA; (F) DWMH-MD.

Figure 3

Associations between the mean FA of the PVWMH-FA penumbra and the composite z-scores of global cognition. Partial r and p-values was obtained after controlling for age, sex, and education.