Quantitative histomorphometry of capillary microstructure in deep white matter.

Area of Science:

• Neuroscience
• Gerontology
• Pathology

Background:

• White matter lesions (WML) are a significant risk factor for dementia in the elderly.
• Cerebral blood flow reduction in WML suggests underlying vascular alterations.
• Microvascular changes, particularly in capillaries, are implicated in dementia but lack quantitative study in white matter.

Purpose of the Study:

• To identify and quantify microstructural changes in capillaries within deep subcortical lesions (DSCL).
• To characterize capillary diameter, thickness, and density in the deep white matter of elderly subjects with and without DSCL.

Main Methods:

• Analysis of deep white matter tissue samples from 75 elderly subjects stratified into Control, Lesion, and Normal Appearing White Matter (NAWM) groups.
• Utilized immunohistochemically-labeled histological images from the Cognitive Function and Aging Study (CFAS).
• Developed and applied a novel semi-automatic method for accurate estimation of capillary dimensions from 2D images, accounting for imaging artifacts.

Main Results:

• Subjects with DSCL showed significantly increased capillary wall thickness.
• A decrease in capillary density was observed in subjects with DSCL.
• Reduced intra-subject variability in capillary diameter, but not the mean diameter, was noted in DSCL groups. No significant differences were found between control and NAWM groups.

Conclusions:

• Capillary wall thickening and reduced capillary density are key microvascular alterations contributing to reduced cerebral blood flow in white matter lesions.
• These quantitative findings provide crucial data for modeling human cerebral blood flow and understanding dementia pathogenesis.