Immune Characterization of Intracranial Aneurysms Using Noninvasive Endoluminal Biopsy With High-Dimensional...

Intracranial aneurysms (IAs) are pathologic dilatations of cerebral arteries with the potential for rupture and subarachnoid hemorrhage (SAH). While inflammation is implicated in IA pathogenesis, the precise immune regulatory mechanisms underlying IA stability, growth, and rupture remain poorly defined. We aimed to characterize the immune landscape of IAs using a noninvasive endoluminal biopsy method coupled with high-dimensional single-cell phenotyping to identify immune signatures associated with IA states.

This prospective observational cohort study was conducted at Yale New Haven Hospital between July 2022 and August 2024. Patients undergoing endovascular treatment for ruptured or unruptured IAs were eligible for inclusion. Endoluminal biopsy samples were obtained using detachable coils and microcatheter tips exposed to the IA lumen during treatment. High-dimensional single-cell phenotyping was performed using mass cytometry by time-of-flight (cyTOF) with a 30-marker panel. Cells were clustered using unsupervised analysis, and immune profiles were compared across IA states. Associations with clinical variables were assessed using Fisher exact tests.

Fifteen patients were included (mean age 52.20 ± 12.42 years; 53.33% female). Smoking history included current (26.67%), former (33.33%), and never (40.00%) smokers. Hypertension was present in 8 patients (53.34%), with 4 controlled and 4 poorly controlled. Sample viability was high (mean 93.28% ± 5.11%). All 6 unstable aneurysms (4 ruptured, 2 unruptured but growing) clustered within cyTOF immune group 1 while 6 of 9 stable or undocumented aneurysms clustered in group 2 (p = 0.01; odds ratio = ∞, 95% CI 1.97-∞). Group 1 exhibited neutrophil predominance and upregulation of CD38, HLA-DR, and CCR7. No significant associations were observed between immune group and rupture status, hypertension, smoking, or laterality.

This study demonstrates that noninvasive endoluminal biopsy combined with high-dimensional single-cell immune phenotyping can identify distinct immune signatures in IAs. A shift toward neutrophil-dominant inflammation was associated with aneurysm growth and rupture. Limitations include the cross-sectional design, which limits causal inference. These findings may support future development of immune-based biomarkers and targeted immunomodulatory therapies to stabilize IAs and prevent rupture.