Article
The correlation between haemodynamics and collagen turnover measured by radiocarbon birth dating as an in-vivo indicator of instability in intracranial aneurysms
Die Korrelation zwischen Hämodynamik und Kollagenumsatz gemessen mittels Radiokarbondatierung als in vivo Indikator für Instabilität in intrakraniellen Aneurysmen
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Published: | May 8, 2019 |
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Objective: Saccular, unruptured intracranial aneurysms (IA) have a prevalence of 3% in the adult population with a mean 5-year risk of rupture of 3.4%, though assessing the rupture risk of an IA of an individual patient remains challenging. Aberrant hemodynamics have been known to play a role in initiation, growth and rupture of IA. However, studies that connect aneurysmal hemodynamics to the biological response from the aneurysmal wall are limited. We previously facilitated radiocarbon (14C) birth dating of the main molecular constituent in walls of IA, i.e. collagen, for assessment of collagen turnover in IA ex-vivo. In this report, we investigated the relation between collagen turnover in IA and aneurysmal hemodynamics to identify hemodynamic parameters indicative of structural instability in patients with IA.
Methods: Aneurysm samples from patients undergoing surgical repair for IA were previously processed and analyzed for collagen age using 14C birth dating. To obtain aneurysmal hemodynamics, 3-dimensional computed tomography angiographic (CTA) data was facilitated for Computational Fluid Dynamics (CFD). Morphologic and hemodynamic parameters were correlated with collagen turnover. Receiver operating characteristic (ROC) analysis was performed for identification of optimal thresholds separating fast from slow/normal collagen turnover for each parameter.
Results: CTA data sufficient in quality for CFD modelling was available in 20 patients (15 female, 5 male) with 6 unruptured and 14 ruptured IA. Collagen turnover was significantly higher in irregular IA compared to regular IA (Mann-Whitney-test, p<0.05) with a significant, negative correlation between collagen turnover and irregularity (r=-0.5, p<0.05). There was a significant, negative correlation between collagen turnover with aneurysmal time-average wall shear stress (WSS) (r=-0.6, p<0.01) and maximum WSS (r=-0.5, p<0.05). ROC analysis demonstrated a good test accuracy (area under the curve of 0.77, 95%CI 0.53–1.0) for average WSS with a threshold of 2.8 dyne/cm2 for fast collagen turnover (sensitivity 92.3%, specificity 57.1%).
Conclusion: Our data constitute the first ever association of actual biological data on chronological tissue turnover in IA with aneurysmal hemodynamics. WSS represents a promising surrogate for rapid collagen turnover indicative of structural instability of IA, possibly serving as a readily available in-vivo surrogate in future. Reconfirming studies are needed for improving the assessment and management of patients with IA.