Development of a second generation intra-sacular cerebral aneurysm flow diverter

描述（由申请人提供）：该项目的长期目标是改善颅内囊状动脉瘤患者的护理，这是自发性动脉瘤破裂或再破裂导致神经系统发病率和死亡率的主要来源。在20世纪90年代早期，由于可拆卸的铂微线圈的发展，这些病人的护理发生了革命性的变化。这些微线圈采用微创、图像引导、导管为基础的技术放置在动脉瘤腔中，避免了许多或大多数患者需要开放手术。尽管与传统手术方法相比，微线圈具有显著的优势，但线圈技术仍然存在重要的缺点。卷绕术的主要缺点仍然是亚急性和慢性动脉瘤再通率高得令人沮丧，在大动脉瘤中高达50%。这种再通不仅使患者面临再出血的风险，而且还面临额外手术的风险，包括血管内手术和开放手术，以期实现永久的动脉瘤闭合。铂微线圈失效的确切生物学机制尚不清楚。然而，最近来自一种全新的栓塞剂的临床前和临床数据，称为“血流分流剂”，表明稳定动脉瘤颈部，而不是像线圈那样填充穹顶，是永久治疗动脉瘤的理想方法。目前的“分流器”是由编织管状结构构成的，与血管内支架的特征相似，但与标准支架相比，其在颈部的金属覆盖率明显更高。这些血流分流器在动物模型和临床病例系列中显示，即使在大动脉瘤中，完全和持久的动脉瘤闭塞率也非常高。不幸的是，由于两个原因，这些管状腔内分流器只能在少数情况下应用。首先，由于它们是腔内装置而不是囊内装置，它们与血栓栓塞事件的高风险相关，需要双重抗血小板治疗，这在急性动脉瘤破裂的情况下是不可取的。其次，腔内分流器目前不能立即实现动脉瘤闭塞，这进一步限制了其在破裂动脉瘤中的应用。最后，这些管状分流器的结构限制了它们在侧壁动脉瘤中的应用，而侧壁动脉瘤不像分叉动脉瘤那样常见。在第一阶段SBIR提案中描述的研究和开发计划将促进引入一种全新的动脉瘤治疗方法：使用“囊内”血流分离器。该装置被称为编织内桥（WEB），将实现有效的血流分流，并且在高概率下，具有极佳的急性和慢性动脉瘤闭塞率。WEB将适用于广泛的动脉瘤形态，将适用于治疗破裂和未破裂的动脉瘤。如果成功，这个SBIR研究计划将大大改变和改善颅内动脉瘤患者的护理。

DESCRIPTION (provided by applicant): The long term objective of this project is to improve the care of patients harboring intracranial, saccular aneurysms, which represent a major source of neurologic morbidity and mortality resulting from spontaneous aneurysm rupture or re-rupture. In the early 1990s the care of these patients was revolutionized by the development of detachable, platinum microcoils. These microcoils are placed into aneurysm cavities using minimally invasive, image guided, catheter based techniques, avoiding the need for open surgery in many or most patients. Notwithstanding the remarkable advantage offered by microcoils over traditional surgical approaches, important shortcomings still remain with coil technology. The primary drawback of coiling remains the frustratingly high rate of subacute and chronic aneurysm recanalization, seen in up to 50% in large aneurysms. Such recanalization not only exposes patients to risk of rebleeding but also to the risk of additional procedures, including both endovascular and open surgical approaches, in hopes of achieving permanent aneurysm closure. The exact biological mechanisms underlying the observed failure of platinum microcoils remain unclear. However, recent preclinical and clinical data from an entirely new class of embolic agents, termed "flow diverters," suggests that stabilizing the aneurysm neck, rather than filling the dome as coils do, is the ideal approach for permanently curing aneurysms. Current "flow diverters" are constructed of braided tubular structures, similar in character to endovascular stents but with markedly higher metallic coverage across the neck as compared to standard stents. These flow diverters have shown in animal models and in clinical case series remarkably high rates of complete and persistent aneurysm occlusion, even in large aneurysms. Unfortunately, these tubular, intraluminal flow diverters can be applied only in a minority of cases for two reasons. First, since they are intraluminal rather than intrasaccular devices they are associated with high risk for thromboembolic events, necessitating administration of dual antiplatelet therapy, which is undesirable in cases of acutely ruptured aneurysms. Second, the intraluminal flow diverters do not at present achieve immediate aneurysm occlusion, which further limits their use in ruptured aneurysms. Finally, the construction of these tubular flow diverters limits their use to side-wall aneurysms, which are less common that bifurcation aneurysm morphologies. The research and development program described in this Phase 1 SBIR proposal will facilitate introduction of an entirely new approach to aneurysm treatment: the use of "endosaccular" flow dividers. This device, termed the Woven EndoBridge (WEB) will achieve efficient flow diversion and, with high probability, excellent rates of acute and chronic aneurysm occlusion. The WEB will be applicable in a wide range of aneurysms morphologies and will be appropriate for treatment of both ruptured and unruptured aneurysms. If successful, this SBIR research program will substantially alter and improve care of patients suffering from intracranial aneurysms. PUBLIC HEALTH RELEVANCE: This research program is aimed at development of a new class of minimally invasive treatment for brain aneurysms, which are an important cause of stroke. The new device developed in this program will improve the safety and effectiveness of aneurysm treatment, without need for open brain surgery.