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

项目摘要： 据估计，脑动脉瘤在一般人群中的患病率为3-7%， 每年增加5%以上，每年造成约50万人死亡。微创神经外科通常 代表了治疗未破裂动脉瘤的最佳手术选择，因为其受益包括缩短长度 与侵入性手术夹闭相比，血管内神经介入治疗依赖于 微导管可安全穿过大脑解剖结构，输送栓塞器械或支架进行动脉瘤治疗。 然而，在许多情况下，曲折的血管系统和几何形状复杂的动脉瘤造成实质性的损伤。 由于无法操纵传统微导管，神经介入医生面临导航挑战 平安导航这种脑血管解剖结构的这些困难导致更长的手术时间， 不成功的导管插入尝试和并发症的风险增加。为了满足临床需求， 神经外科微导管，克服了这些可移植性相关的障碍，我们建议工程师 并评估具有集成微流体电路的3D纳米打印软机器人微导管， 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。 我们的首要假设是，通过利用和扩展机器交叉领域的最新进展， 基于学习的设计、添加剂纳米制造、集成微流体电路和软微机器人， 新型的远程可操纵神经外科微导管可以以前所未有的规模实现， 克服当前基于可操作性的缺陷，并最终提高导管插入术的有效性、安全性和 脑动脉瘤的治疗结果。我们将调查这一假设的临床可行性 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 告知软机器人微导管的操作性能。在第二章中，我们将研究... 3D纳米打印多致动器尖端和集成微流体回路的制造效率， 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计划相关要求。在目标3中，我们将开发一款手持设备， 控制器的神经介入医生，并比较软机器人微型， 导管与标准临床微导管的比较，使用基于以下的脑血管解剖体外模型 患者特异性临床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。 机器人微导管（即，相对于标准临床微导管）， 动物模型中的血管内神经介入术（犬，n=8）。如果成功，拟议的3D纳米打印 软机器人微导管具有独特的前景，不仅用于治疗脑动脉瘤， 而且还适用于目前被认为具有挑战性或高风险的广泛血管内介入治疗，因为体积小， 复杂的、曲折的和/或脆弱的脉管系统，例如用于治疗小儿先天性心脏缺陷。

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.