부산대학교 도서관

Objective: Periventricular white matter hyperintensities (pvWMHs) are commonly observed on MRI in older individuals and are associated with cognitive and motor decline. The etiology of pvWMH remains unknown. Venous collagenosis has been implicated, which may also interfere with perivascular fluid flow leading to dilation of perivascular spaces (PVS). Here, we examine relationships between in vivo pvWMH volume and ex vivo morphological quantification of collagenosis and the PVS in veins and arteries. Methods: Brain tissue from 25 Oregon Alzheimer's Disease Research Center subjects was selected to cover the full range of WMH burden. Tissue from white matter abutting the ventricle was stained with Masson's trichrome and smooth muscle actin. An automated hue based algorithm identified and segmented vessel into collagenized vessel walls, lumen, and PVS. Multiple linear regressions with pvWMH volume as the dependent variable and either collagen thickness or PVS width were performed with covariates of vessel diameter, age at death, sex, and interval between MRI and death. Results: PVS width and collagen thickness were significantly correlated in both arteries (r = 0.21, p = 0.001) and veins (r = 0.23, p = 0.001). Increased venous collagen (p = 0.017) was a significant predictor of higher pvWMH burden while arterial collagen was not (p = 0.128). Neither PVS width in arteries (p = 0.937) nor veins (p = 0.133) predicted pvWMH burden. Interpretation: These findings are consistent with a model in which venous collagenosis mediates the relationship between vascular risk factors and pvWMH. This study confirms the importance of changes to the venous system in contributing to MRI white matter lesions commonly observed with advanced age. ANN NEUROL 2022;92:992–1000 Summary for Social Media: White matter hyperintensities are a common MRI finding in the aged population and are associated with risk of stroke, mild cognitive impairment, dementia, and overall mortality. While likely vascular in origin, the precise mechanisms by which they develop remain elusive. White matter hyperintensities may be caused by deposition of collagen in veins and consequently be related to the size of the periventricular space. Our results show that while collagen deposition in veins is correlated with the size of the periventricular space, only collagenosis was predictive of white matter hyperintensity burden. This study confirms the importance of changes to the venous system in contributing to MRI white matter lesions commonly observed with advanced age and presents an underexplored biological mechanism by which these changes may impact health. [ABSTRACT FROM AUTHOR]