MR-Guided Precision Conformal Ablation Therapy for Brain Tumors

项目摘要 脑转移瘤（BM）是全身性癌症最常见的转移部位，发病率高达 在北美每年新增17万例。未经治疗的BM患者通常活不到两个月。 目前的治疗选择仅限于切除手术、放射疗法和化学疗法。热 消融术已被假定为替代疗法，但可用的装置具有显著的局限性， 关于消融图案的适形空间控制和进入脑内的一些区域。这个项目 建议开发针式治疗超声（NBTU）设备和集成系统， 精确靶向和诱导适形消融模式，用于治疗肿瘤并在大型动物中验证 模型项目初期开发了一套完整的工具， 磁共振成像引导机器人辅助（MRGRA）输送间质NBTU作为神经消融剂 该设备，最终在两个猪生存手术的日期。该NBTU设备提供的优势超过 经颅高强度聚焦超声，因为可以靶向大脑的所有区域，消融体积可以成形为三个- 同时进行活检是可能的。这个竞争性的更新项目将集中在需要， 修改器械，为首次人体试验做准备，并在重要的动物研究中验证器械。的 本项目的目标是：1）开发定向治疗超声探头， 沿长度和角度沿着产生受控的能量强度分布以允许保形消融 基于肿瘤体积的模式。2)优化机器人递送设备设计，以最大限度地提高其可达性 工作空间，并通过在不同的大脑区域进行消融来验证这种能力。3)改善界面 当前FDA 510 K批准的TheraVision治疗计划和监测系统、MR热 磁共振成像（MRTI）和MR引导的机器人辅助设备，以允许“点击”软件使用;以及4）在 根据FDA对首次人体试验的要求，确认该系统的临床就绪版本 通过进行监测安全性和准确性的存活猪研究，在适当的设计控制下。一个 FDA IDE申请将在本项目的最后阶段提交，为未来的首次人体临床试验做准备。 审判该项目的成功完成将导致实质性的技术和可行性的进步， HIFU的当前最新技术水平，包括体积MR热成像和定制的NBTU探头 和给药策略。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，附带损伤最小， 周围的非目标组织。

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.