3D-Nanoprinted Soft Robotic Microcatheters with Integrated Microfluidic Circuitry for Cerebrovascular Surgery

项目总结： 据估计，脑动脉瘤在3%-7%的普通人群中很普遍，而且病例还在增加。 每年增长超过5%-导致每年约500,000人死亡。微创神经外科通常 是治疗未破裂动脉瘤的最佳手术选择，因为它的好处包括缩短长度 与侵入性手术夹闭相比，减少了停留时间和并发症。血管内神经干预依赖于 微导管可以安全地穿过大脑解剖结构，为动脉瘤治疗提供栓塞器或支架。 然而，在许多情况下，曲折的血管和几何复杂的动脉瘤构成了实质性的 神经干预者因无法操纵常规微导管而面临的导航挑战 安全无恙。导航这种脑血管解剖的这些困难导致了更长的程序时间， 插管尝试不成功，并发症风险增加。为了满足临床需求， 克服这些可操作性相关障碍的神经外科微导管，我们建议设计 并使用集成微流控电路作为一种手段来评估3D纳米打印软式机器人微导管 在血管内神经介入治疗期间实现按需、多方向转向和导航控制。 我们最重要的假设是，通过利用和扩展机器交叉点的最新进展 基于学习的设计、添加纳米制造、集成微流控电路和软微机器人， 新型可远程引导的神经外科微导管可以以前所未有的规模实现 克服目前基于可操作性的缺陷，并最终提高导尿术的有效性、安全性和 脑动脉瘤的治疗结果。我们将研究这一假说的临床可行性。 通过四个具体目标。在目标1中，我们将创建基于机器学习的设计技术，用于预测和 告知软式机器人微导管的操作性能。在目标2中，我们将研究Manu- 3D纳米打印多驱动器针尖和集成微流控电路的制造效率 作为完全统一的软机器人微导管，能够按需进行多方向变形 基础设施和外部控制方案相关要求。在目标3中，我们将开发一款手持设备 为神经干预者提供控制器，并比较软机器人微控制器的机动性效果。 导管与标准临床微导管相比，采用体外脑血管解剖学模型 患者特有的临床3D血管造影图像。在目标4中，我们将评估软件的可行性和安全性 通过微创进行机器人微导管(即相对于标准临床微导管) 血管内神经介入动物模型(犬，n=8)。如果成功，建议的3D纳米打印 软式机器人微导管拥有独特的前景，不仅在治疗脑动脉瘤方面具有变革性， 也适用于目前被认为具有挑战性或高风险的大范围血管内介入治疗， 复杂的、曲折的和/或微妙的血管结构，如用于治疗儿童先天性心脏病。

Project Summary: Cerebral aneurysms are estimated to be prevalent in 3–7% of the general population—with cases increasing by more than 5% each year—resulting in ~500,000 deaths annually. Minimally invasive neurosurgery typically represents the best surgical option for treating unruptured aneurysms due to benefits including reduced length of stay and complications compared to invasive surgical clipping. Endovascular neurointerventions rely on microcatheters to traverse cerebral anatomy safely to deliver embolic devices or stents for aneurysm treatment. In many cases, however, tortuous vasculature and geometrically complex aneurysms pose substantial navigation challenges for neurointerventionalists due to an inability to maneuver conventional microcatheters safely. These difficulties in navigating such cerebrovascular anatomies contribute to longer procedural times, unsuccessful catheterization attempts, and increased risks of complications. To address the clinical need for neurosurgical microcatheters that overcome these maneuverability-associated barriers, we propose to engineer and evaluate 3D-nanoprinted soft robotic microcatheters with integrated microfluidic circuitry as a means to enable on-demand, multi-directional steering and navigation control during endovascular neurointerventions. Our overarching hypothesis is that, by leveraging and extending recent advances at the intersection of machine learning-based design, additive nanomanufacturing, integrated microfluidic circuitry, and soft microrobotics, novel classes of remotely steerable neurosurgical microcatheters can be realized at unprecedented scales to surmount current maneuverability-based deficits, and ultimately, improve catheterization efficacy, safety, and outcomes in the treatment of cerebral aneurysms. We will investigate the clinical feasibility of this hypothesis through four specific aims. In Aim 1, we will create machine learning-based design techniques for predicting and informing the operational performance of the soft robotic microcatheter. In Aim 2, we will examine the manu- facturing efficacy for 3D nanoprinting multi-actuator tips and integrated microfluidic circuits both independently and as fully unified soft robotic microcatheters capable of on-demand, multi-directional deformations with minimal infrastructure and external control scheme-associated requirements. In Aim 3, we will develop a handheld controller for the neurointerventionalist and compare the maneuverability efficacy of the soft robotic micro- catheter to that of standard clinical microcatheters using in vitro models of cerebrovascular anatomy based on patient-specific clinical 3D angiography images. In Aim 4, we will assess the feasibility and safety of the soft robotic microcatheter (i.e., with respect to standard clinical microcatheters) by performing minimally invasive endovascular neurointerventions in animal models (canine, n=8). If successful, the proposed 3D-nanoprinted soft robotic microcatheters hold unique promise to be transformative not only for treating cerebral aneurysms, but also for wide-ranging endovascular interventions currently considered challenging or high risk due to small, complex, tortuous, and/or delicate vasculature, such as for the treatment of pediatric congenital heart defects.