Oliver, Alexander A

Purpose Large aneurysms have a higher rupture risk, yet no available in vivo animal model consistently produces large aneurysms for testing endovascular therapies. Recent research suggests that adding calcium chloride (CaCl 2 ) to elastase yields larger aneurysms in a surgical rabbit model. We evaluated whether this effect translates to an endovascular approach by comparing aneurysm sizes created using elastase alone versus a CaCl 2 –elastase combination. Methods Aneurysms were created in the right common carotid artery of New Zealand rabbits. One group received 1 mL porcine elastase; the other received elastase plus 0.055 g CaCl 2 (0.5 M). After four weeks, patency was confirmed via digital subtraction angiography. Two blinded co-authors measured the neck, width, and height of the aneurysms. Aneurysm volumes were estimated using AngioCalc.com. Statistical analyses were performed using either the Mann–Whitney U -test or t -test based on data distribution. Results Twenty-nine (29) New Zealand rabbits were included in the study: six in the CaCl 2 and elastase groups, 23 in the elastase-alone group. All induced aneurysms remained patent at follow-up. Mean neck size was significantly larger in the CaCl 2 + elastase group than in the elastase-alone group (4.4 ± 1.1 mm vs 3.5 ± 0.95 mm; respectively, p = 0.02). Differences in width (4.1 ± 0.92 mm vs 3.4 ± 0.36 mm; p = 0.06), height (9.0 ± 1.1 mm vs 9.1 ± 2.1 mm; p = 0.46), and volume (83.5 ± 38.35 mm ³ vs 53.0 ± 16.94 mm³; p = 0.11) were not significant between CaCl 2 + elastase and elastase-alone, respectively. Conclusions CaCl 2 modestly increased neck size but did not significantly enlarge overall aneurysm dimensions. Further studies are needed to assess its utility in endovascular aneurysm models.

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

We have developed a cost-effective method to study the fate of stents, particularly flow diverter stents placed in the abdominal aorta, in a rat model. This technique utilizes (caudal) tail artery access,1–5 thereby avoiding the need for surgical exposure of the femoral or carotid arteries and reducing procedural invasiveness,6 7 aligning with the principles of refinement and reduction in animal research.7 This approach may be particularly beneficial for studies requiring multiple or iterative vascular access. The use of ultrasound guidance further reduces costs and infrastructure requirements by eliminating the need for specialized angiography suites.8 This makes this technique accessible to a broader range of research settings, promoting wider adoption and collaboration in the field of endovascular research. A detailed demonstration of this method is provided in the accompanying educational video (video 1). Video 1 -Technical video describing the tail artery access and flow diverter deployment using ultrasound guidance.

Background: Traumatic carotid artery pseudoaneurysms (PSAs) represent a vascular anomaly with potential for serious complications, including stroke. Traditional treatments involve endovascular stenting, which may not be ideally suited to otherwise healthy vessels that have the potential to remodel. Given the limitations of smaller animal models in replicating human vasculature and the need for improved treatment modalities, this study introduces a novel swine model for the creation and evaluation of carotid PSAs. Methods: The PSAs were created from bovine dura and anastomosed in an end-to-side fashion to bilateral carotid arteries. The PSAs were radiologically followed up post-operatively and were harvested at 3 and 10 days for histological analysis. Results: Pseudoaneurysms were successfully created in both animals without intra-operative or immediate post-operative complications. Radiological analysis showed well-perfused PSAs with intra-aneurysmal turbulence, hemodynamically mimicking human carotid artery PSAs. There was no evidence of thrombus or arterial stenosis. Histological examinations revealed thrombus maturation and tight anastomosis of the PSA sac with the native artery. Conclusions: This PSA swine model offers a replicable, cost-effective, and easily implemented tool with the potential to advance carotid PSA management and educational efforts in vascular surgery. Clinical Impact The model presented in this methodology paper allows for a standardized PSA animal model allowing for the standardization of a clinical entity which is frequently heterogenenous in morphology. This can allow for the development of new therapies or provide a ground truth for computer modelling for further in silico study.

Background Although flow diverters (FDs) have benefited from several technical improvements, recently concerns have arisen regarding the braid stability after implantation. Thus, we investigated frequency, predictive factors, and clinical impact of the phenomenon of FD braid deformation (FDBD). Methods Consecutive intracranial aneurysms (IAs) treated with various FDs, between January 2018 and July 2023, were reviewed to identify FDBD (defined as the deformation of a FD without any external force applied to it). Patient, aneurysm, procedural, and FD characteristics were retrieved and analyzed using univariate and multivariable analyses. Morbidity is defined as a score of +1 in the modified Rankin Scale at 3 months. Results In total, 245 FD procedures (271 FDs implanted; 25 multiple IAs treated with 1 FD) in 228 patients; FDBD was observed in 36/245 cases (14.7%), mainly at follow-up angiography (32/36, 88.9%); fish-mouthing was the most frequent FDBD. Morbidity was related to fish-mouthing and braid collapse and was significantly higher in the FDBD group after retreatment (p=0.04). Drawn filled tubing with platinum (DFT) (adjusted odds ratio (aOR)=7.0, 95% CI 3.0 to 17.5; p<0.001) and FD diameter (aOR=2.2, 95% CI 1.3 to 4.1; p<0.01) were identified as independent predictors of FDBD. The metal alloy composing the FD (p=0.13) and coated surfaces were not significantly associated with FDBD (p=0.54 in multivariable analysis). Conclusions FDBD is a frequent phenomenon observed in about 15% of cases, and it was responsible for higher morbidity. Only FD characteristics (DFT and FD diameter) were independent determinants of FDBD. Future research should focus on the impact of novel braid configurations and materials on braid stability.

OBJECTIVE Fibrin deposition represents a key step in aneurysm occlusion, promoting endothelization of implants and connective tissue organization as part of the aneurysm-healing mechanism. In this study, the authors introduce a novel in vitro testing platform for flow diverters based on human fibrinogen. METHODS A flow diverter was deployed in 4 different glass models. The glass models had the same internal parent artery (4 mm) and aneurysm (8 mm) diameters with varying parent artery angulations (paraophthalmic, sidewall, bifurcation, and slightly curved models). The neck size and area were 4 mm and 25 mm 2 , respectively. Human fibrinogen (330 mg/dl) was circulated within the glass models at varying flow rates (0, 3, 4, and 5 ml/sec) with or without heparin, calcium chloride, and thrombin for as long as 6 hours or until complete fibrin coverage of the flow diverter’s neck was achieved. Aneurysm neck coverage was defined as macroscopic fibrin deposition occluding the flow diverters’ pores. Flow characteristics after flow diverter deployment were assessed with computational fluid dynamics analysis. The effects of flow rates, heparin, calcium chloride, and thrombin on fibrin deposition rates were tested using 1-way ANOVA and the Tukey test. RESULTS A total of 84 replicates were performed. Human fibrin did not accumulate on the flow diverter stents under static conditions. The fibrin deposition rate on the aneurysm neck was significantly greater with the 5 ml/sec flow rate as compared to 3 ml/sec for all models. The paraophthalmic model had the highest inflow velocity of 48.7 cm/sec. The bifurcation model had the highest maximum shear stress (SS) and maximum normalized shear stress values at the device cells at 843.3 dyne/cm 2 and 35.1 SS/SS inflow , respectively. The fibrin deposition rates of the paraophthalmic and bifurcation models were significantly higher than those of sidewall and slightly curved models for all additive or flow rate comparisons (p = 0.001 for all comparisons). The incorporation of thrombin significantly increased the fibrin deposition rates across all models (p = 0.001 for all models). CONCLUSIONS Rates of fibrin deposition varied widely across different configurations and additive conditions in this novel in vitro model system. Fibrin accumulation started at the aneurysm inflow zone where flow velocity and shear stress were the highest. The primary factors influencing fibrin deposition included flow velocities, shear stress, and the addition of thrombin at a physiological concentration. Further research is needed to test the clinical utility of fibrinogen-based models for patient-specific aneurysms.

The New Zealand rabbit elastase-induced arterial aneurysm of the right common carotid artery remains a widely used model for assessing the effectiveness and safety of new neuroendovascular devices.1 This model offers a simple and reliable platform for pre-clinical in vivo investigations, crucial for comprehending the biological processes underlying aneurysm healing after endovascular treatment.2 Notably, the induced aneurysm exhibits morphological, hemodynamic, and histological characteristics similar to human intracranial aneurysms. The creation of the aneurysm is performed using open and endovascular techniques. Each step of the procedure requires a meticulous and controlled gesture to ensure reproducibility of the aneurysm and minimize animal misuse. In video 1 we present a step-by-step procedural guide for aneurysm creation and follow-up. We hope this resource will help in promoting this model and provide useful guidance for researchers in the field. Video 1 Surgical procedure of creating elastase-induced aneurysms in rabbits.

Background Although direct contact aspiration has emerged as one of the leading techniques for mechanical thrombectomy (MT), there is still ongoing debate about the aspiration/suction pump devices that can optimize recanalization rates. To address this gap, we conducted a meta-analysis comparing the aspiration efficacy of 60 ml syringe and pump devices in benchtop MT models. Methods Systematic literature review was conducted using Medline, Embase, Web of Science, and Scopus in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Outcomes of interest included flow rate and vacuum pressure delivered by a 60 ml syringe and several aspiration pumps. We used a random effects model to calculate the mean difference (MD) with 95% confidence intervals (CIs) and a statistically significant difference was considered as a two-sided p -value of less than 0.05. Results We included six benchtop studies comparing 60 ml syringes and vacuum pumps. Our meta-analysis showed that there were no significant differences in vacuum pressure (MD:0.71inHg, 95% CI: [−0.81;2.23], p = 0.359) and flow rate (MD:0.27 mL/s, 95% CI: [−3,07; 3.61], p = 0.873) between 60 ml syringes and vacuum pumps groups. Conclusions Our study demonstrated comparable performance in terms of vacuum pressure and flow rates between a 60 ml syringe and a heterogeneous combination of commercially available aspiration pumps.

Platinum-containing stents are commonly used in humans with hypercholesterolemia, whereas preclinical stent evaluation has commonly been performed in healthy animal models, providing inadequate information about stent performance under hypercholesterolemic conditions. In this investigation, we used an ApoE−/− mouse model to test the impact of hypercholesterolemia on neointima formation on platinum-containing implants. We implanted 125 μm diameter platinum wires into the abdominal aortas of ApoE−/− and ApoE+/+ mice for 6 months, followed by histological and immunofluorescence examination of neointimal size and composition. It was found that ApoE−/− mice developed neointimas with four times larger area and ten times greater thickness than ApoE+/+ counterparts. Neointimas developed in the ApoE−/− mice also contained higher amounts of lipids quantified as having 370 times more coverage compared to ApoE+/+, a 3-fold increase in SMCs, and a 22-fold increase in macrophages. A confluent endothelium had regenerated in both mouse strains. The ApoE−/− mice experienced luminal reductions more closely resembling clinically relevant restenosis in humans. Overall, the response to platinum arterial implants was highly dependent upon the atherogenic environment.

OBJECTIVE Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.