Efficacy and Safety of a Novel Flow Disruptor Device in a Rabbit Elastase-induced Aneurysm Model

다국어 초록 (Multilingual Abstract)

Purpose: Flow disruptor devices have been recently developed for placement entirely within the aneurysmal cavity. Although flow disruptors have been designed in various shapes, including spherical and hemispherical, which have shown success and promise in treating aneurysms, the variety of shapes and types remains limited. This study aimed to evaluate the efficacy and safety of a novel flow disruptor (NFD), designed to function as both a flow diverter and disruptor, in a rabbit aneurysm model.

Materials and Methods: The NFD aneurysm embolization device was braided using double layer of 144 interwoven nitinol wire with 30 μm thickness, and platinum markers were fixed at both proximal and distal ends to identify the device. The lower part of the NFD was designed to divert blood flow by increasing the protrusion in the direction of the parent artery in bifurcating cerebral aneurysms, with a proximal part cone angle set at approximately 15°. The devices were manufactured with 5 mm x 2.5 mm and 6 mm x 3 mm. Elastase-induced aneurysms were created in 21 rabbits and treated with the NFD. Animals were randomly assigned to follow-up evaluations at 1 month (n = 7), 2 months (n = 7), and 3 months (n = 7). Angiographic and histological analyses were performed to assess aneurysm occlusion rates and neointimal formation.

Results: All embolization procedures were technically successful without procedural-related complications, and all animals survived until the end of the study. Immediate angiography demonstrated near-complete or complete flow disruption in 52% of aneurysms. Follow-up angiography at 1 and 3 months revealed near-complete or complete occlusion 71% in 5 aneurysms. Follow-up angiography revealed favorable aneurysm occlusion rates, reaching 85% in 6 aneurysms at 2 months. NFD protrusion was identified 48% in 10 cases during angiographic follow-up. Histologically, successful neointimal formation across the aneurysm neck was observed when the device was appropriately implanted in the aneurysmal sac with connective tissue and organized thrombus. However, regarding the intentional device tip protrusion observed in 10 cases of NFD protrusion, 6 (60%) showed incomplete occlusion demonstrated among 10 cases of NFD protrusion, while in 4 (40%) cases, near-complete occlusion was achieved when the protruding tip of NFD was embedded in the arterial wall, providing neointima formation.

Conclusion: The NFD demonstrated promising aneurysm occlusion rates and safety in a rabbit aneurysm model when appropriate wall apposition and tip embedding were achieved. Nevertheless, the intended protrusion design feature produced inconsistent effects due to anatomical limitations of the rabbit elastase-induced aneurysm model. Further studies with refined delivery systems, advanced imaging, and diverse aneurysm models are warranted to validate and optimize the clinical potential of the NFD.

목차 (Table of Contents)

• ABSTRACT i
• CONTENTS iii
• LIST OF FIGURES iv
• LIST OF TABLES vi
• LIST OF ABBREVIATIONS vii
• INTRODUCTION 1
• MATERIALS AND METHODS 5
• 1. Preparation of a new flow disruptor 5
• 2. Computational fluid dynamics (CFD) simulation of blood flow velocity 8
• 3. Animal study 15
• 4. Elastase-induced aneurysm creation 17
• 5. Animal experiments 20
• 6. NFD safety analysis 23
• 7. Angiography analysis 24
• 8. Histological examination 25
• RESULTS 26
• 1. Simulated blood flow velocity 26
• 2. Procedural outcomes 36
• 3. Angiographic findings 39
• 4. Histological findings 44
• DISCUSSION 47
• CONCLUSION 56
• REFERENCE 57
• 국문요약 66