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

描述（由申请方提供）：本项目的长期目标是改善颅内囊性动脉瘤患者的护理，囊性动脉瘤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，由于可分离铂微弹簧圈的开发，这些患者的护理发生了革命性的变化。使用微创、图像引导、基于导管的技术将这些微弹簧圈置入动脉瘤腔内，避免了许多或大多数患者需要开放手术。尽管微弹簧圈相对于传统手术方法具有显著优势，但弹簧圈技术仍存在重要缺点。弹簧圈栓塞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，在大型动脉瘤中高达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，包括血管内和开放手术方法，以期实现永久性动脉瘤闭合。观察到的铂微弹簧圈失效的确切生物学机制尚不清楚。然而，最近的临床前和临床数据表明，一种全新的栓塞剂，称为“血流导向器”，稳定动脉瘤颈，而不是像弹簧圈那样填充圆顶，是永久治愈动脉瘤的理想方法。目前的“血流导向装置”由编织管状结构构成，其特征与血管内支架相似，但与标准支架相比，其颈部的金属覆盖率明显更高。这些血流导向装置在动物模型和临床病例系列中显示出非常高的动脉瘤完全和持续闭塞率，即使在大动脉瘤中也是如此。不幸的是，由于两个原因，这些管状的管腔内流动转向器只能应用于少数情况。首先，由于它们是管腔内而不是囊内器械，因此与血栓栓塞事件的高风险相关，需要给予双重抗血小板治疗，这在急性破裂动脉瘤的情况下是不可取的。其次，腔内血流导向装置目前不能实现动脉瘤的立即闭塞，这进一步限制了其在破裂动脉瘤中的使用。最后，这些管状血流导向装置的结构限制了其对侧壁动脉瘤的使用，侧壁动脉瘤比分叉部动脉瘤形态更不常见。本SBIR 1期提案中描述的研发计划将促进引入一种全新的动脉瘤治疗方法：使用“囊内”分流器。这种被称为Woven EndoBridge（WEB）的器械将实现有效的血流导向，并且极有可能实现极高的急性和慢性动脉瘤闭塞率。WEB将适用于各种动脉瘤形态，并适用于破裂和未破裂动脉瘤的治疗。如果成功的话，SBIR研究计划将大大改变和改善颅内动脉瘤患者的护理。 公共卫生相关性：这项研究计划旨在开发一种新的微创治疗脑动脉瘤的方法，脑动脉瘤是中风的重要原因。该项目中开发的新设备将提高动脉瘤治疗的安全性和有效性，而无需开放性脑手术。

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.