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.

Abstract

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.