Figure 5
Vascular network length, microglia density and vascular inflammation in WMH and NAWM. (a) (Sub-)segmentation of both normal-appearing white matter (NAWM) and white matter hyperintensity (WMH) based on changes on fluid-attenuated inversion recovery (FLAIR) signal. (b) Representative voxel-wise image of vascular network length (GLUT1 glucose transporter 1) analyzed across tissue blocks immunolabeled and cleared with a modified iDISCO+ protocol. In WMH (white dashed line; n = 294), vascular network length was approximately 30% shorter compared to NAWM (p < 0.001; n = 664). Vascular network length showed a negative correlation with WMH (sub-)segmentation (ρ = − 0.272; p < 0.001), suggesting underlying vascular network architecture was shorter with increasing MRI signal. (c) Representative voxel-wise image of microglia density (IBA1 ionized calcium-binding adaptor molecule 1). The amount of microglia per mm3 in WMH (white dashed line) was larger than NAWM (p < 0.001). (d) Representative voxel-wise image of vascular inflammation (colocalization between IBA1 and GLUT1). Colocalization analysis showed that vascular inflammation was larger in NAWM than WMH (p < 0.001). Min–max normalization was used for the data shown in (b–d). GM grey matter, scale bars, 1 cm (a–d).
