A novel intracranial exchange guidewire improves the navigation of various endovascular devices: An in vitro study of challenging situations

Objective Neuroendovascular procedures rely on successful navigation and stable access to the target vessel. The Stabilizer is a 300 cm long exchange wire with a 0.014 diameter and a soft, flexible stent at the distal end designed to assist with navigation and device delivery. This study aims to assess the efficacy of the Stabilizer for navigation in a variety of challenging environments. Methods The efficacy of the Stabilizer was evaluated using three challenging vascular models: a giant aneurysm model, a severe tortuosity model, and an M1 stenosis model. The Stabilizer was compared with a conventional wire during navigation in each model. Results In the giant aneurysm model, there was no significant difference of success during straightening of a looped wire and significantly higher success rates when advancing an intermediate catheter with the Stabilizer beyond the aneurysm neck compared to a conventional guidewire. The Stabilizer also significantly increased success rates when advancing an intermediate catheter through a model with severe tortuosity compared to a conventional guidewire, as well as exchange maneuver for intracranial stenting in a stenosis model compared to an exchange wire. Conclusions In our experimental model, the Stabilizer significantly improved navigation and device delivery in a variety of challenging settings compared to conventional wires.

GP.3 Examining Aneurysmal Healing After Flow Diversion Treatment Using Endovascular Optical Coherence Tomography

Background: The mechanism of aneurysmal healing after flow-diversion treatment of cerebral aneurysms remains unknown. The purpose of this research to is to utilize a novel technology called endovascular optical coherence tomography (OCT) to characterise and improve our understanding of aneurysmal healing after flow-diversion using a rabbit aneurysm model. Methods: Saccular aneurysms were created in 10 New Zealand white rabbits. The aneurysms were treated with a flow-diverting stent 28 days after creation. OCT and histopathologic examinations included: luminal thrombosis, endothelial loss, inflammation, fibrin, smooth muscle cell loss, disruption of the internal and external elastic lamina, and tunica adventitia changes Results: OCT revealed endothelialization across the stent, appearing to originate from the parent vessel, along with small amounts of thrombus on the stent-struts. Minimal thrombus was visualized within the aneurysm sac. Histologic examination revealed that OCT can accurately define endothelialization across the sent, and define patent segments across the neck. Conclusions: Aneurysmal healing appears to originate at the parent vessel/stent interface, and use the stent as a scaffold to grow across the neck of the aneurysm. Minimal thrombus was visualized within the aneurysm sac, with ongoing flow observed in the setting of incomplete neck endothelialization. This technology has great potential for assessing aneurysmal healing in real-time.

Computational Study of Hemodynamic Changes Induced by Overlapping and Compacting of Stents and Flow Diverter in Cerebral Aneurysms

Purpose: The flow diversion effect of an intracranial stent is closely related to its metal coverage rate (MCR). In this study, the flow diversion effects of Enterprise and low-profile visualized intraluminal support (LVIS) stents are compared with those of a Pipeline flow diverter, focusing on the MCR change. Moreover, the changes in the flow diversion effect caused by the additional manipulations of overlapping and compaction are verified using computational fluid dynamics (CFD) analysis.Methods: CFD analysis was performed using virtually generated stents mounted in an idealized aneurysm model. First, the flow diversion effects of single Enterprise, LVIS, and Pipeline devices were analyzed. The Enterprise and LVIS were sequentially overlapped and compared with a Pipeline, to evaluate the effect of stent overlapping. The effect of compacting a stent was evaluated by comparing the flow diversion effects of a single and two compacted LVIS with those of two overlapped, uncompacted LVIS and uncompacted and compacted Pipeline. Quantitative analysis was performed to evaluate the hemodynamic parameters of energy loss, average velocity, and inflow rate.Results: Statistically significant correlations were observed between the reduction rates of the hemodynamic parameters and MCR. The single LVIS without compaction induced a reduction in all the hemodynamic parameters comparable to those of the three overlapped Enterprise. Moreover, the two overlapped, uncompacted LVIS showed a flow diversion effect as large as that induced by the single uncompacted Pipeline. Compacted stents induced a better flow diversion effect than uncompacted stents. The single compacted LVIS induced a flow diversion effect similar to that induced by the two uncompacted LVIS or single uncompacted Pipeline.Conclusions: The MCR of a stent correlates with its flow diversion effect. Overlapping and compaction can increase the MCR of an intracranial stent and achieve a flow diversion effect as large as that observed with a flow diverter.

Application of a rabbit-elastase aneurysm model for preliminary histology assessment of the PPODA-QT liquid embolic

Background: PPODA-QT is a novel liquid embolic under development for the treatment of cerebral aneurysms. We sought to test the rabbit-elastase aneurysm model to evaluate the tissue response following PPODA-QT embolization. Methods: Experimental elastase-induced aneurysms were created in fourteen New Zealand White Rabbits. Eight animals were used for aneurysm model and endovascular embolization technique development. Six PPODA-QT-treated animals were enrolled in the study. Control and aneurysm tissues were harvested at acute (n = 2), 1-month (n = 2), and 3-month (n = 2) timepoints and the tissues were prepared for histology assessment. Results: All fourteen rabbit-elastase aneurysms resulted in small and medium aneurysm heights (<10 mm dome height) with highly variable neck morphologies, small midline dome diameters, and beyond-wide dome-to-neck (d: n) ratios. Histological evaluation of four aneurysms, treated with PPODA-QT, demonstrated reorganization of aneurysm wall elastin into a smooth muscle layer, and observed as early as the 1-month survival timepoint. At the aneurysm neck, a homogenous neointimal layer (200–300 μm) formed at the PPODA-QT interface, sealing off the parent vessel from the aneurysm dome. No adverse immune response was evident at 1- and 3-month survival timepoints. Conclusion: PPODA-QT successfully embolized the treated aneurysms. Following PPODA-QT embolization, neointimal tissue growth and remodeling were noted with minimal immunological response. The experimental aneurysms created in rabbits were uniformly small with inconsistent neck morphology. Further testing of PPODA-QT will be conducted in larger aneurysm models for device delivery optimization and aneurysm healing assessment before human clinical investigation.

Aneurysm severity is suppressed by deletion of CCN4

Patients with abdominal aortic aneurysms are frequently treated with high-risk surgery. A pharmaceutical treatment to reverse aneurysm progression could prevent the need for surgery and save both lives and healthcare resources. Since CCN4 regulates cell migration, proliferation and apoptosis, processes involved in aneurysm progression, it is a potential regulator of aneurysm progression. We investigated the role of CCN4 in a mouse aneurysm model, using apolipoprotein-E knockout (ApoE−/−) mice fed high fat diet and infused with Angiotensin II (AngII). Blood pressure was similarly elevated in CCN4−/−ApoE−/− mice and CCN4+/+ApoE−/− mice (controls) in response to AngII infusion. Deletion of CCN4 significantly reduced the number of ruptured aortae, both thoracic and abdominal aortic area, and aneurysm grade score, compared to controls. Additionally, the frequency of vessel wall remodelling and the number of elastic lamina breaks was significantly suppressed in CCN4−/−ApoE−/− mice compared to controls. Immunohistochemistry revealed a significantly lower proportion of macrophages, while the proportion of smooth muscle cells was not affected by the deletion of CCN4. There was also a reduction in both proliferation and apoptosis in CCN4−/−ApoE−/− mice compared to controls. In vitro studies showed that CCN4 significantly increased monocyte adhesion beyond that seen with TNFα and stimulated macrophage migration by more than threefold. In summary, absence of CCN4 reduced aneurysm severity and improved aortic integrity, which may be the result of reduced macrophage infiltration and cell apoptosis. Inhibition of CCN4 could offer a potential therapeutic approach for the treatment of aneurysms.

Application of Proper Orthogonal Decomposition to Study Coherent Flow Structures in a Saccular Aneurysm

Aneurysms are localized expansions of weakened blood vessels that can be debilitating or fatal upon rupture. Previous studies have shown that flow in an aneurysm exhibits complex flow structures that are correlated with its inflow conditions. Therefore, the objective of this study was to demonstrate the application of proper orthogonal decomposition (POD) to study the impact of different inflow conditions on energetic flow structures and their temporal behavior in an aneurysm. To achieve this objective, experiments were performed on an idealized rigid sidewall aneurysm model. A piston pump system was used for precise inflow control, i.e., peak Reynolds number (Rep) and Womersley number (α) were varied from 50 to 270 and 2 to 5, respectively. The velocity flow field measurements at the midplane location of the idealized aneurysm model were performed using particle image velocimetry (PIV). The results demonstrate the efficacy of POD in decomposing complex data, and POD was able to capture the energetic flow structures unique to each studied inflow condition. Furthermore, the time-varying coefficient results highlighted the interplay between the coefficients and their corresponding POD modes, which in turn helped explain how POD modes impact certain flow features. The low-order reconstruction results were able to capture the flow evolution and provide information on complex flow in an aneurysm. The POD and low-order reconstruction results also indicated that vortex formation, evolution, and convection varied with an increase in α, while vortex strength and formation of secondary structures were correlated with an increase in Rep.