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Published on: March 7, 2019
Clustering of Cerebral Microbleeds in Cerebral Amyloid Angiopathy: A Flow Territory-Based Analysis
Manon R Schipper1, Reinier G J van der Zwet2, Jelle J Goeman3
1Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Background:
Cerebral microbleeds (CMBs) are a key imaging marker of cerebral amyloid angiopathy (CAA), but their individual spatial distribution and potential clustering remain poorly understood.
Purpose:
This study assessed whether CMBs exhibit patient-specific, flow territory-based clustering in sporadic (sCAA) and Dutch-type hereditary CAA (D-CAA). The arterial flow territory subdivision was chosen, considering the predilection of CMB location in the posterior cortex-not limited to the occipital lobe-and the prominent vascular role in CAA.
Study Type:
Retrospective cross-sectional study.
Population:
Thirty-three participants (17 (52%) female, 65 ± 12 years old, 19 sCAA; 14 D-CAA) without symptomatic intracerebral hemorrhage (sICH) and ≥ 1 CMB were included for the main analysis.
Field Strength/Sequence:
3 T MRI susceptibility-weighted imaging, multi-echo 3D gradient echo.
Assessment:
Spatial CMB patterns were evaluated by comparing observed versus expected CMB density within covariate-matched subgroups, accounting for age, sex, CAA-type, smoking, and hypertension. CMBs were manually annotated and assigned to six arterial flow territories (left/right ACA, MCA, PCA) using a standardized atlas. A sensitivity analysis was performed on all participants (including sICH+ participants).
Statistical Tests:
Expected values were calculated by multiplying flow territory CMB proportions per covariate-matched subgroup. Unweighted individual chi-square statistics were calculated, and statistical significance was assessed via permutation testing (10,000 replications) per covariate group.
Results:
Across covariate-matched subgroups, observed CMB counts significantly deviated from expected distributions, indicating substantial interindividual variability and within-participant clustering (χ2 = 6920). The effect remained significant when including sICH+ participants (χ2 = 102,027, n = 85; 44 sCAA; 41 D-CAA). CMB densities differed across flow territories, with highest median densities in the right PCA, right MCA, and left PCA (0.173 (IQR = 0.387), 0.121 (IQR = 0.238), and 0.113 (IQR = 0.389) counts per cm3, respectively).
Data Conclusion:
These findings indicate CMBs in CAA are not identically distributed but show patient-specific clustering within flow territories, suggesting variable regional vulnerability, potentially influenced by local pathology or vascular anatomy.
Evidence Level:
1.
Technical Efficacy:
Stage 2.
Insights
Cerebral microbleeds (CMBs) in cerebral amyloid angiopathy (CAA) show patient-specific clustering within arterial territories. This suggests varying regional vulnerability, not uniform distribution, in sporadic and Dutch-type CAA.
Area of Science:
- Neurology
- Radiology
- Vascular Biology
Background:
- Cerebral microbleeds (CMBs) are key imaging markers of cerebral amyloid angiopathy (CAA).
- The spatial distribution and clustering of CMBs in CAA are not well understood.
- Understanding CMB patterns may reveal insights into CAA pathogenesis.
Purpose of the Study:
- To investigate patient-specific, flow territory-based clustering of CMBs in sporadic (sCAA) and Dutch-type hereditary CAA (D-CAA).
- To analyze CMB distribution within arterial territories, considering the posterior cortex predilection and vascular role in CAA.
Main Methods:
- Retrospective cross-sectional study of 33 participants (19 sCAA, 14 D-CAA) with CMBs using 3T MRI.
- CMBs were manually annotated and assigned to six arterial flow territories (ACA, MCA, PCA).
- Observed CMB density was compared to expected distributions using permutation testing, accounting for covariates.
Main Results:
- CMB counts significantly deviated from expected distributions, revealing substantial interindividual variability and within-participant clustering.
- CMB densities varied across flow territories, with the highest median densities observed in the right PCA, right MCA, and left PCA.
- Findings remained significant in sensitivity analysis including participants with symptomatic intracerebral hemorrhage.
Conclusions:
- CMBs in CAA exhibit patient-specific clustering within arterial flow territories.
- This clustering suggests variable regional vulnerability in the brain, potentially linked to local pathology or vascular anatomy.
- The distribution of CMBs is not uniform, highlighting individual differences in CAA progression.
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