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Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images
Published on: November 20, 2015
MRI contrast accumulation in features of cerebral small vessel disease: blood-brain barrier dysfunction or elevated
Tomas Vikner1,2,3, Anders Garpebring4, Cecilia Björnfot4,5
1Department of Diagnostics and Intervention, Umeå University, Umeå, SE, S-90187, Sweden. tomas.vikner@umu.se.
Background:
White matter lesions (WML) and dilated perivascular spaces (PVS) are features of small vessel disease (SVD), commonly observed in aging and dementia, with unknown pathophysiology. Human studies have documented contrast accumulation within and in proximity of SVD-lesions. However, whether such observations mainly reflect excessive blood-brain barrier (BBB) leakage, or altered microvascular density in the investigated regions, remains unclear.
Methods:
To evaluate the roles of BBB leakage and vascular density in aging and SVD, dynamic contrast enhanced (DCE) MRI was used to estimate the permeability-surface area product (PS) and fractional plasma volume ([Formula: see text]) in normal-appearing brain tissue and in proximity of and within WML and PVS in a population-based cohort (N = 56; 34/22 m/f; age 64 to 84 years). Analysis of variance (ANOVA) was used to assess regional differences in PS and [Formula: see text] and analysis of covariance (ANCOVA) was used to assess regional differences in PS with [Formula: see text] and vascular risk as covariates.
Results:
Pronounced increases in PS and [Formula: see text] were observed from normal-appearing white matter (NAWM) to WML peripheries to WMLs. Similar PS and [Formula: see text]increases were observed from basal ganglia (BG) to BG-PVS. Further, PS in NAWM and white matter (WM) PVS were found to increase with cortex-to-ventricular depth. However, ANCOVA models with [Formula: see text] as a covariate showed that variance in PS was mainly explained by vp (η2=0.17 to η2=0.35; all p < 10- 3), whereas the effect of region was only borderline-significant when comparing NAWM, WML peripheries and WML (p = 0.03) and non-significant for the other comparisons (p > 0.29).
Conclusions:
Our findings support the notion that contrast leakage across the BBB accumulates within and in proximity of SVD-related lesions. However, high contrast accumulation may mainly reflect high vascularization, and to a lesser degree than previously recognized BBB dysfunction.
Insights
Small vessel disease (SVD) lesions show increased contrast accumulation, primarily due to higher vascularization rather than blood-brain barrier (BBB) leakage. This finding impacts our understanding of SVD pathophysiology in aging and dementia.
Area of Science:
- Neuroimaging
- Cerebrovascular Diseases
- Aging and Dementia Research
Background:
- White matter lesions (WML) and dilated perivascular spaces (PVS) are hallmarks of small vessel disease (SVD), prevalent in aging and dementia.
- The underlying pathophysiology of SVD, particularly the role of blood-brain barrier (BBB) integrity versus microvascular changes, remains incompletely understood.
- Previous studies noted contrast accumulation in SVD lesions, but the primary cause—BBB leakage or altered vascularity—was unclear.
Purpose of the Study:
- To investigate the contributions of blood-brain barrier (BBB) leakage and altered vascular density to SVD manifestations.
- To differentiate between BBB permeability and vascular volume as drivers of contrast enhancement in SVD lesions and related structures.
Main Methods:
- Dynamic contrast-enhanced (DCE) MRI was employed in a population-based cohort (N=56, ages 64-84) to quantify permeability-surface area product (PS) and fractional plasma volume (vp).
- Measurements were taken in normal-appearing white matter (NAWM), within and around white matter lesions (WML), and in basal ganglia (BG) and perivascular spaces (PVS).
- Statistical analyses, including ANOVA and ANCOVA, were used to assess regional differences and the influence of vascular volume and risk factors on BBB permeability.
Main Results:
- Significant increases in both PS and vp were observed from NAWM to WML peripheries and into WMLs, and similarly from BG to BG-PVS.
- PS in NAWM and white matter PVS increased with greater cortex-to-ventricular depth.
- Multivariate analysis revealed that vascular volume (vp) predominantly explained the variance in PS, with regional differences being less significant, suggesting vascularization plays a larger role than BBB dysfunction.
Conclusions:
- Contrast accumulation in and around SVD lesions is confirmed, but it is primarily attributed to increased vascularization (vp) rather than solely to blood-brain barrier (BBB) dysfunction.
- These findings suggest that altered microvascular density is a more significant factor than previously recognized in the contrast enhancement observed in SVD.
- The study refines the understanding of SVD pathophysiology, emphasizing the role of vascular changes in imaging findings.
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