MINIR-II: Minimally Invasive Neurosurgical Intracranial Robot

描述（由申请人提供）：这个R01项目建立在一个非常成功的R21项目的基础上，该项目涉及使用形状记忆合金（SMA）致动器的微创神经外科颅内机器人（MINIR-I）的开发和可行性，以及在连续MRI下对该设备进行评估，用于切除猪脑中植入的“转移性肿瘤”。虽然我们实现了R21项目的具体目标，但我们也发现了新的挑战，这是R01应用程序的基础。脑肿瘤是癌症最可怕的并发症之一，发生在20-40%的成年癌症患者中。尽管治疗取得了许多进展，但这些患者的预后很差，中位生存期为4-8个月。无论是原发性（内在的）恶性肿瘤，还是继发性（转移性的）恶性肿瘤，对癌症患者的大脑的影响都是毁灭性的，因为它威胁到个体的个性和身份，并且总是最可能直接严重影响生活质量的并发症。目前，大多数脑肿瘤的最佳治疗方法是手术切除，以促进放疗和化疗等辅助治疗。不幸的是，由于病变位置不利（通常为深部或传统神经外科技术无法到达），以及患者一般健康状况不佳，许多患者不能接受脑肿瘤的原发性手术切除。为了解决这个问题，基于我们的R21试点项目的成功，以及从中吸取的经验教训，我们建议开发一种完全兼容MRI的MINIR-II，并通过对临床相关的离体和体内猪以及随后的人体尸体模型的综合评估来证明MINIR-II的安全性和有效性。正如设想的那样，MINIR-II将在医生的直接控制下，目标信息完全来自实时MRI，使用内置MINIR-II传感器的主动靶向方法。为实现mini - ii，我们将实现四个具体目标：1)设计一个完全兼容MRI的多自由度（DOF） MINIR-II刚性塑料体，具有电缆驱动的关节，用于布线和电子设备的中空内芯，灌溉和吸吸能力，以及肿瘤切除能力。2)开发和表征一个多片模具，能够成型几何形状复杂的机器人链接，具有微型特征，以生产一个完全一次性/一次性的MINIR-II原型。3)开发MINIR-II的跟踪和导航系统，使其能够可视化近端和远端结构，以准确定位和切除肿瘤；最后4)MINIR-II在明胶幻影和转移性脑肿瘤的临床相关模型中的安全性和有效性，包括尸体猪模型、活猪模型和人尸体模型。在这个项目结束时，我们的目标是让mini - ii（在连续MRI下操作）为临床试验做好准备。

DESCRIPTION (provided by applicant): This R01 project builds on a highly successful R21 project which involved the development and feasibility of a Minimally Invasive Neurosurgical Intracranial Robot (MINIR-I) using shape memory alloy (SMA) actuators as well as the evaluation of the device under continuous MRI for resection of an implanted "metastatic tumor" in swine brain. While we achieved the specific aims of the R21 project, we also discovered new challenges, which are the basis for this R01 application. Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients. Despite numerous advances in treatment, the prognosis for these patients is poor, with a median survival of 4-8 months. Whether a primary (intrinsic) malignancy, or a secondary (metastatic) malignancy, involvement of the brain in a cancer patient is devastating, because it threatens the very personality and identity of the individual, and is invariably the most likely of all complications o directly and severely affect the quality of life. Currently, the optimal treatment for most brain tumors involves primary surgical resection to facilitate adjuvant therapies such as radiation and chemotherapy. Unfortunately, many patients cannot undergo primary surgical resection of their brain tumor due to unfavorable location of the lesion (usually deep or otherwise inaccessible to conventional neurosurgical techniques), and poor general health of the patient. To address this problem, based on the success of our R21 pilot project, and the lessons learned therein, we propose to develop a fully MRI- compatible MINIR-II and demonstrate the safety and efficacy of MINIR-II through comprehensive assessments on clinically relevant ex vivo and in vivo swine and followed by human cadaver models. As envisioned, MINIR-II will be under the direct control of the physician, with targeting information obtained exclusively from real-time MRI that uses active targeting methods with the sensors embedded within MINIR-II. To realize MINIR-II, we will address four specific aims: 1) Design a fully MRI compatible multiple degree-of-freedom (DOF) MINIR-II of rigid plastic body with cable driven joints, hollow inner core for routing cablin and electronics, irrigation and suction capability, and tumor removal capability, 2) Develop and characterize a multi-piece mold capable of molding geometrically complex robot links with miniature features to produce a completely disposable/single use MINIR-II prototype, 3) Develop a tracking and navigation system for MINIR-II that will allow visualization of proximal and distal structures for accurate targeting and resection of the tumor, and finally 4) the safety and efficacy of MINIR-II in gelatin phantoms and clinically relevant models of metastatic brain tumor including, a cadaveric pig model, a live pig model, and a human cadaver model. Our goal at the end of this project is to have MINIR-II (operated under continuous MRI) ready for clinical trials.