Effects of the flow diversion technique on nucleotide levels in intra-cranial aneurysms: A feasibility study providing new research perspectives

Abstract

Introduction: The flow diverter stent (FDS) has become a first-line treatment for numerous intra-cranial aneurysms (IAs) by promoting aneurysm thrombosis. However, the biological phenomena underlying its efficacy remain unknown. We proposed a method to collect in situ blood samples to explore the flow diversion effect within the aneurysm sac. In this feasibility study, we assessed the plasma levels of nucleotides within the aneurysm sac before and after flow diversion treatment.

Materials and methods: In total, 14 patients with unruptured IAs who were selected for FDS implantation were prospectively recruited from February 2015 to November 2015. Two catheters dedicated to (1) FDS deployment and (2) the aneurysm sac were used to collect blood samples within the parent artery (P1) and the aneurysm sac before (P2) and after (P3) flow diversion treatment. The plasma levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) at each collection point were quantified with liquid chromatography and tandem mass spectrometry.

Results: The aneurysms were extradural in nine (64.3%) patients and intra-dural in five (35.7%) patients. They presented an average diameter of 15.5 ± 7.1 mm, height of 15.8 ± 4.6 mm, and volume of 2,549 ± 2,794 ml. In all patients (100%), 16 FDS implantations and 42 in situ blood collections were performed successfully without any complications associated with the procedure. The ATP, ADP, and AMP concentrations within the aneurysm sac were decreased after flow diversion (p = 0.005, p = 0.03, and p = 0.12, respectively). Only the ATP levels within the aneurysm sac after flow diversion were significantly correlated with aneurysm volume (adjusted R ² = 0.43; p = 0.01).

Conclusion: In situ blood collection within unruptured IAs during a flow diversion procedure is feasible and safe. Our results suggest that the flow diversion technique is associated with changes in the nucleotide plasma levels within the aneurysm sac.

Keywords: flow diversion; in situ blood collection; intra-cranial aneurysm; nucleotides; thrombosis – etiology.

FIGURE 1

Illustrates the different steps of the blood collection within the parent vessel and the aneurysm sac during the endovascular treatment with the flow diverter stent.

FIGURE 2

Illustrates a patient presenting a giant aneurysm of the right internal carotid artery (segment C4; red asterisk; A–E). The 0.027-inch catheter for the first blood collectio (P1) is visible in panels (B–E) (single black arrow). The 0.021-inch catheter within the aneurysm sac is visible in panels (B–E) (double black arrows). The flow diverter stent is deployed in panels (C–E) (triple black arrows).

FIGURE 3

The boxplot shows the results of the measured AMP levels (in μM) within the parent vessels (P1) and the aneurysm sacs before (P2) and after (P3) flow diversion. No significant differences were observed for the AMP levels between the three sampling locations.

FIGURE 4

The boxplot shows the results of the measured ADP levels (in μM) within the parent vessel (P1) and the aneurysm sac before (P2) and after (P3) flow diversion. The ADP levels were significantly lower within the aneurysm sacs after flow diversion (P3) compared to the ones in the parent vessels (P1) (p = 0.008).

FIGURE 5

The boxplot shows the results of the measured ATP levels (in μM) within the parent vessel (P1) and the aneurysm sac before (P2) and after (P3) flow diversion. The AMP levels were significantly lower within the aneurysm sacs before (P2) and after (P3) flow diversion compared to the ones in the parent vessels (P1) (p = 0.018 between P1 and P2, and p = 0.003 between P1 and P3).

FIGURE 6

The scatter plot reports the ATP levels (in μM) within the aneurysm sacs after flow diversion (P3) according to the aneurysm volumes (in mm3). A significant correlation was observed between the ATP levels within the aneurysm sacs after flow diversion (P3) and the aneurysm volumes (R² = 0.44; p = 0.014).