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

描述(申请人提供)：该项目的长期目标是改善对患有颅内囊状动脉瘤的患者的护理，这些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。20世纪90年代初，随着可拆卸铂微线圈的开发，这些患者的护理发生了革命性的变化。这些微弹簧圈使用微创、图像引导、基于导管的技术被放置到动脉瘤腔中，从而避免了许多或大多数患者需要开放手术。尽管微弹簧圈与传统手术方法相比具有显著的优势，但弹簧圈技术仍然存在重大缺陷。弹簧圈的主要缺点仍然是令人沮丧的亚急性和慢性动脉瘤再通率，在大型动脉瘤中可见高达50%。这种再通不仅使患者面临再次出血的风险，而且还面临额外手术的风险，包括血管内和开放手术途径，以期实现动脉瘤的永久闭合。所观察到的铂微线圈失效背后的确切生物学机制尚不清楚。然而，最近来自一种全新类型的栓塞剂的临床前和临床数据表明，稳定动脉瘤颈部，而不是像弹簧圈那样填充穹顶，是永久治愈动脉瘤的理想方法。目前的“分流管”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，其颈部金属覆盖率明显更高。这些分流装置已经在动物模型和临床病例系列中显示出非常高的完全和持续性动脉瘤闭塞率，即使在大型动脉瘤中也是如此。不幸的是，这些管状的腔内分流装置只能在少数情况下使用，原因有两个。首先，由于它们是腔内装置而不是门静脉内装置，它们与血栓栓塞事件的高风险相关，因此需要进行双重抗血小板治疗，这在急性破裂的动脉瘤病例中是不可取的。其次，腔内分流装置目前还不能立即闭塞动脉瘤，这进一步限制了它们在破裂动脉瘤中的应用。最后，这些管状分流装置的结构限制了它们对侧壁动脉瘤的使用，侧壁动脉瘤比分叉动脉瘤的形态更少见。第一阶段SBIR提案中描述的研究和开发计划将有助于引入一种全新的动脉瘤治疗方法：使用“囊内”血流分隔器。这种被称为编织内桥(Web)的装置将实现有效的血流分流，并极有可能实现极高的急性和慢性动脉瘤闭塞率。WEB将适用于广泛的动脉瘤形态，并将适合于治疗破裂和未破裂的动脉瘤。如果成功，这项SBIR研究计划将极大地改变和改善对患有颅内动脉瘤的患者的护理。 公共卫生相关性：这项研究计划旨在开发一种新的脑动脉瘤微创治疗方法，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，而不需要开放脑部手术。

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.