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.

Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated meta-analysis

“…Seven of the 27 newly identified cross-sectional studies investigated patients with cognitive impairment or dementia; including Alzheimer’s disease (AD), 18, 19 mild cognitive impairment (MCI) 8, 10, 20 and vascular cognitive impairment (VCI). 9, 21…”

“…Since 2016, several studies have been published that provide data on regional or tissue-specific CBF in WMH and normal appearing white matter (NAWM) cross-sectionally, [6][7][8][9][10] as well as longitudinal studies. Therefore, we updated our previous systematic review and meta-analysis 3 to identify whether these gaps in the literature and previous inconsistencies have been resolved.…”

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

“…This matter of fact most likely depends on the severity of the SVD (2, 9-11) and the exact disease stage (9,10,12,(40)(41)(42). WMH may present with impaired blood brain barrier, loss of oligodendrocytes and reduced density of glia, vacuolation and axonal damage and impaired white matter integrity as reported on diffusion tensor imaging (2,9,10,12,(43)(44)(45). However, as in MSL, conventional MRI does not allow for a differentiation of histologically different WMH (4,5).…”

Loss of Integrity of Corpus Callosum White Matter Hyperintensity Penumbra Predicts Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment

“…FA and MD maps of each subject were first coregistered to the corresponding individual T1 3D-SPGR image using the b0 image and then smoothed with a 6 mm full width at half-maximum Gaussian kernel, then resliced into a 2 × 2 × 2 mm 3 voxel-size matrix. According to the previous studies and our recent work (Promjunyakul et al, 2015 , 2016 ; Wu et al, 2019 ), the size of FA and MD penumbras of PVWMH and DWMH were as follows: 6 mm for both FA and MD penumbras of PVWMH, 4 mm for the FA penumbra of DWMH, and 2 mm for the MD penumbra of DWMH. The FA and MD penumbras was gained by summing the FA or MD penumbra of PVWMH and DWMH.…”

“…Furthermore, changes in NAWM were found to be associated with a decline in cognitive function as determined by diffusion tensor imaging (DTI; Huang et al, 2007 ; Papma et al, 2014 ; Hirsiger et al, 2017 ). NAWM surrounding WMHs that can only be detected on a microstructural level is referred to as the WMH-penumbra (WMH-P; Maillard et al, 2011 ); neuroimaging studies have revealed damage below the detection threshold in these non-lesioned WM areas (Promjunyakul et al, 2015 , 2016 ; Wu et al, 2019 ). WMH does not fully explain the neuroimaging correlates of cognitive decline in SVCI, as histopathologic alterations in the WMH-P can also lead to CI (Simpson et al, 2007 ; Gouw et al, 2011 ; Promjunyakul et al, 2015 ); however, as these changes are subtle, it may be possible to prevent their aggravation through early intervention.…”