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BACKGROUND: Bioresorbable polymer-based flow-diverting stents have potential benefits over existing metal devices. This study aimed to evaluate the safety and efficacy of the novel ReSolv device, which is a primarily polymer-based flow-diverting stent, using the in vivo rabbit sidewall saccular aneurysm model. METHODS: ReSolv stents were deployed in 14 New Zealand White rabbits that had undergone aneurysm creation procedures. Animals were allocated to follow-up time points of 1, 3, 6, 9, 12, 16, or 18 months. Angiographic images were evaluated by an independent neurointerventionalist blinded to follow-up time points for (1) in-stent stenosis, (2) parent vessel and jailed side branch patency, (3) wall apposition, and (4) aneurysm occlusion using the Raymond-Roy Occlusion Classification (RROC), O'Kelly Marotta grading scale, and the 4F flow diversion predictive score. Primary efficacy outcome was defined as RROC Class I or II. RESULTS: At a median follow-up time of 7.5 months, parent vessel (14/14) and jailed side (33/33) branches were patent in all cases. There was no development of thrombus on the stent or cases of significant in-stent stenosis, and all stents had good wall apposition. Adequate occlusion was found in 85.7% (n = 12) of animals, including an RROC Class I in 64.3% (n = 9) and RROC Class II in 21.4% (n = 3). CONCLUSIONS: The ReSolv stent shows encouraging angiographic safety and efficacy outcomes after placement in a rabbit sidewall saccular aneurysm model. Longer term studies are ongoing to determine eventual fate of the aneurysm, parent vessel, and jailed side branches after absorption of the polymer component of the stent.
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BACKGROUND: Flow-diverting stents are not currently indicated for the treatment of bifurcation aneurysms, and some case series have demonstrated low occlusion rates, possibly due to a lack in neck coverage. The ReSolv stent is a unique hybrid metal/polymer stent that can be deployed with the shelf technique in order to improve neck coverage. METHODS: A Pipeline, unshelfed ReSolv, and shelfed ReSolv stent were deployed in the left-sided branch of an idealized bifurcation aneurysm model. After determining stent porosity, high-speed digital subtraction angiography runs were acquired under pulsatile flow conditions. Time-density curves were created using two region of interest (ROI) paradigms (total aneurysm and left/right), and four parameters were extracted to characterize flow diversion performance. RESULTS: The shelfed ReSolv stent demonstrated better aneurysm outflow alterations compared to the Pipeline and unshelfed ReSolv stent when using the total aneurysm as the ROI. On the left side of the aneurysm, there was no significant difference between the shelfed ReSolv stent and the Pipeline. On the right side of the aneurysm, however, the shelfed ReSolv stent had a significantly better contrast washout profile than the unshelfed ReSolv stent and the Pipeline stent. CONCLUSIONS: The ReSolv stent with the shelf technique demonstrates the potential to improve flow diversion outcomes for bifurcation aneurysms. Further in vivo testing will help to determine whether the additional neck coverage leads to better neointimal scaffolding and long-term aneurysm occlusion.
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Embolización Terapéutica , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Stents , Angiografía de Substracción Digital , Resultado del Tratamiento , Angiografía CerebralRESUMEN
OBJECTIVE: Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device. METHODS: Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system. RESULTS: The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups. CONCLUSIONS: The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.
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BACKGROUND: Unruptured intracranial aneurysms (UIA) are increasingly being treated by endovascular coiling as opposed to open surgical clipping. Unfortunately, endovascular coiling imparts an approximate 25% recanalization rate, leading to additional procedures and increased rupture risk. While a new health technology innovation (HTI) that reduces this recanalization rate would benefit patients, few advancements have been made. We aim to determine whether cost-effectiveness has been a barrier to HTI. METHODS: A probabilistic Markov model was constructed from the healthcare payer perspective to compare standard endovascular treatment of UIA to standard treatment plus the addition of a HTI adjunct. Costs were measured in 2018 USD and health outcomes were measured in quality-adjusted life-years (QALY). In the base case, the HTI was a theoretical mesenchymal stem cell therapy which reduced the aneurysm recanalization rate by 50% and cost $10,000 per procedure. All other model inputs were derived from the published scientific literature. RESULTS: Based on the model results, we found that for a given HTI price (y) and relative risk reduction of aneurysm recanalization (x), the HTI was always cost-effective if the following equation was satisfied: y ≤ 20268 â x, using a willingness-to-pay threshold of $50,000 per QALY. The uncertainty surrounding whether an aneurysm would recanalize was a significant driver within the model. When the uncertainty around the risk of aneurysm recanalization was eliminated, the 10-year projected additional benefit to the United States healthcare system was calculated to be $113,336,994. CONCLUSION: Cost-effectiveness does not appear to be a barrier to innovation in reducing the recanalization rate of UIA treated by endovascular coil embolization. Our model can now be utilized by academia and industry to accentuate economically feasible HTI and by healthcare payers to calculate their maximum willingness-to-pay for a new technology. Our results also indicate that predicting a patient's baseline risk of aneurysm recanalization is a critical area of future research.
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Análisis Costo-Beneficio , Aneurisma Intracraneal , Embolización Terapéutica , Procedimientos Endovasculares , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Creating aneurysm sizes in animal models that resemble human aneurysms is essential to study and test neuroendovascular devices. The commonly used rabbit surgical elastase model, however, produces saccular aneurysms that are smaller than those typically treated in humans. The goal of this study was to determine whether an increased vessel stump length and the addition of calcium chloride to the incubation solution has an effect on the resulting aneurysm size. METHODS: Using a modified aneurysm creation method, 32 female New Zealand White rabbits underwent aneurysm creation procedures. Subjects were equally allocated into 4 different groups based on vessel stump length (2 cm controls vs. 3 cm) and incubation solution (elastase alone controls vs. a 1:1 mixture of elastase and calcium chloride). At 4 weeks, all animals underwent angiography to determine the resulting aneurysm size by a neurointerventionalist who was blinded to treatment group. RESULTS: An increase in stump length from 2 cm to 3 cm resulted in a significant increase in the height of aneurysm (P < 0.05). Compared with control animals, the combination of a 3-cm stump length and the addition of calcium chloride to the incubation solution resulted in a significant increase in aneurysm height, width, and volume (P < 0.05). CONCLUSIONS: Creating larger aneurysms is necessary for the rabbit model to be more clinically relevant. Our study demonstrated that the utilization of a 3-cm vessel stump as well as both calcium chloride and elastase in the incubation solution results in aneurysm sizes that more closely resemble the population of aneurysms treated in humans.
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Aneurisma Intracraneal/inducido químicamente , Aneurisma Intracraneal/diagnóstico por imagen , Modelos Anatómicos , Elastasa Pancreática , Algoritmos , Angiografía de Substracción Digital , Animales , Cloruro de Calcio/farmacología , Arteria Carótida Común , Angiografía Cerebral , Femenino , Humanos , Aneurisma Intracraneal/cirugía , ConejosRESUMEN
BACKGROUND: Aneurysm recurrence after Pipeline Embolization Device (PED) placement can be caused by oversizing of the stent as well as poor wall apposition, both of which can lead to elongation. The objective of this study was to assess whether a novel parameter for measuring device elongation based on two-dimensional imaging could be predictive for persistent aneurysm filling after treatment with the PED. METHODS: A retrospective cohort analysis was initially completed on 41 aneurysms from institution A, examining demographic, aneurysmal, and device measurements. Device measurements, including the ratio of the measured length to the nominal length (ML/NL) of the PED, were taken by reviewers blinded to the primary end point, which was aneurysm occlusion status on 6 month catheter angiogram. Findings were then externally validated against 30 aneurysms (supraclinoid only) from institution B. RESULTS: Data from institution A showed 61% complete aneurysm occlusion at 6 months, and were lower for aneurysms in the supraclinoid region. For supraclinoid aneurysms alone, combined data from both institutions showed higher rates of nonocclusion with aneurysm neck size >4 mm (P = 0.008) and a trend toward significance in aneurysms with a branch vessel (P = 0.051). The mean ML/NL ratio was significantly larger in the nonoccluded group compared with the occluded group at both institution A (ratio, 1.37 versus 1.10; P < 0.001) and institution B (ratio, 1.36 vs. 1.11; P = 0.002). CONCLUSIONS: Our data suggest that a novel parameter based on two-dimensional angiography may serve as a rapid technique to measure device elongation and predict occlusion of supraclinoid aneurysms after PED placement.
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Angiografía Cerebral/métodos , Embolización Terapéutica/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Neuroimagen/métodos , Adulto , Estudios de Cohortes , Embolización Terapéutica/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosRESUMEN
Several studies have demonstrated a potential interaction between mesenchymal stem cells (MSCs) and saccular aneurysms. In this study, we sought to determine whether allogenic bone marrow-derived MSCs had the ability to prevent aneurysm formation in a known rabbit elastase aneurysm model. MSCs were injected intravenously in experimental rabbits at the time of surgical creation and two weeks postcreation and compared with control rabbits receiving vehicle injection. Angiography was used to compare aneurysm measurements four weeks postcreation, and aneurysms were harvested for histological properties. Serum was collected longitudinally to evaluate cytokine alterations. Serum from control animals was also utilized to perform in vitro tests with MSCs to compare the effect of the serologic environment in animals with and without aneurysms on MSC proliferation and cytokine production. While aneurysm morphometric comparisons revealed no differences, significant cytokine alterations were observed in vitro and in vivo, suggesting both anti-inflammatory and proinflammatory processes were occurring in the presence of MSCs. Histological analyses suggested that tunica intima hyperplasia was inhibited in the presence of MSCs.