Abstract

Introduction: The time required for intracranial aneurysms (IAs) to develop until their diagnosis is unknown. We used a novel method of vascular radiocarbon birth dating of collagen extracted from aneurysms of patients undergoing surgical repair of ruptured and unruptured IAs to estimate their ages. Methods: Between 03/2009 and 04/2013, 46 aneurysm samples from 43 patients were obtained. Collagen was extracted and purified after pepsin digestion of IA tissue. and accelerator mass spectrometry was used to measure 14 C levels in the collagen samples. The age of the aneurysm collagen was estimated and then correlated with patient age, incidence of modifiable risk factors for aneurysm progression, IA rupture status and morphological measurements. Findings: Nearly all collagen in cerebral aneurysms was five or less years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, IAs from patients with a history of risk factors for aneurysm formation (smoking and hypertension) contained significantly younger collagen, as compared to patients with no risk factors (mean 1·6 ± 1·2 years vs. 3·9 ± 3·3 years, respectively, p= 0·012). Interpretation: We show that chronological development of IAs can be consistently estimated, that they are relatively young when detected, and/or that there is constant collagen remodelling within them. In either case, the results suggest there are no cerebral aneurysms that are stable and old. Furthermore, aneurysm age or collagen turnover is significantly more rapid in patients with modifiable risk factors for aneurysm progression and rupture. These results have important implications for the understanding of the biology of cerebral aneurysms as well as for recommendations for follow-up of patients with unruptured cerebral aneurysms.

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