Clustering of Cerebral Microbleeds in Cerebral Amyloid Angiopathy: A Flow Territory-Based Analysis.

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.