MR-Guided Precision Conformal Ablation Therapy for Brain Tumors

项目摘要 脑转移(BM)是系统性癌症最常见的转移部位，其发病率为 到北美每年新增病例17万例。未经治疗的BM患者通常存活不到两个月。 目前的治疗选择仅限于切除手术、放射治疗和化疗。热能 消融已经被认为是一种替代疗法，但现有的设备在以下方面存在显著限制 关于消融模式和进入大脑某些区域的共形空间控制。这个项目 建议开发针基治疗性超声(NBTU)设备和集成系统，以 精确靶向和诱导适形消融模式在大动物肿瘤治疗中的应用及验证 模特。最初的项目阶段导致开发了一套完整的工具，这些工具利用实时 磁共振成像引导机器人辅助(MRgRA)间质NBTU作为神经消融剂的输送 装置，到目前为止，这最终导致了两次猪存活手术。此NBTU设备具有以下优势 经颅HIFU在大脑的所有区域都可以靶向，消融体积可以塑造三个- 从维度上讲，同时进行活检是可能的。此竞争性更新项目将重点关注以下需求 修改该设备，为首次人体试验做准备，并在一项重要的动物实验中验证该设备。这个 该项目的目标是：1)开发定向治疗性超声探头，其配置为 沿长度和角度产生受控的能量强度分布，以允许适形消融 基于肿瘤体积的模式。2)优化机器人送货装置设计，最大限度地提高其可达性 工作空间，并通过在不同大脑区域进行消融来验证这一能力。3)完善界面 在目前FDA 510K批准的TheraVision治疗计划和监测系统之间， 成像(MRTI)和MR引导的机器人辅助设备，以实现软件的“点击”使用；以及4) 根据FDA对首个人试验的要求，验证该系统的临床就绪版本 在适当的设计控制下，通过实施监测安全性和准确性的存活猪研究。一个 FDA的IDE申请将在该项目的最后阶段提交，为未来的第一个人类临床做准备 审判。该项目的成功完成将带来技术和可行性方面的重大进步 目前最先进的HIFU，包括体积磁共振热成像和定制的NBTU探头 以及给药策略。该项目将直接导致交付一种新的高精度治疗方案 脑转移患者将提供靶向肿瘤消融，并对 包围着非靶标组织。

Project Summary Brain metastases (BM) are the most common site of metastases from systemic cancer, with an incidence of up to 170,000 new cases per year in North America. Untreated BM patients generally live less than two months. Treatment options are currently limited to resective surgery, radiation therapies and chemotherapy. Thermal ablation has been postulated as an alternative therapy, but available devices have significant limitations with respect to conformal spatial control of ablation pattern and access to some regions within the brain. This project proposes development of needle-based therapeutic ultrasound (NBTU) devices and integrated system to accurately target and induce conformal ablation patterns for treatment of tumors and validation in a large animal model. The initial project period resulted in the development of a complete set of tools that utilize real-time magnetic resonance imaging guided robot-assisted (MRgRA) delivery of interstitial NBTU as a neuroablative device, which culminated in two swine survival surgeries to date. This NBTU device offers advantages over transcranial HIFU in that all regions of the brain can be targeted, ablation volumes can be shaped three- dimensionally, and concurrent biopsy is possible. This competitive renewal project will focus on the need to modify the device to prepare for first-in-human trials and to validate the device in a significant animal study. The objectives of this project are to: 1) Develop directional therapeutic ultrasound probes that are configured to produce controlled intensity distribution of energy along both length and angle to allow for conformal ablation patterns based on tumor volume. 2) Optimize the robotic delivery device design to maximize its reachable workspace, and validate this capacity by performing ablations in various brain regions. 3) Improve the interface between the current FDA 510K approved TheraVision therapy planning and monitoring system, MR thermal imaging (MRTI), and MR-guided robotic assist device to allow for “point and click” software use; and 4) In accordance with FDA requirements for a first in man trial, validate the clinically ready version of this system under appropriate design controls by performing survival swine studies that monitor safety and accuracy. An FDA IDE application will be filed in the final stages of this project to prepare for a future first-in-human clinical trial. Successful completion of this project will result in substantial technical and feasibility advancements over the current state-of-the-art for HIFU, including volumetric MR thermal imaging and customized NBTU probes and dosing strategies. This project will lead directly to delivery of a new high-precision treatment option for patients with brain metastases that will provide targeted tumor ablation with minimal collateral damage to surrounding non-targeted tissue.