MR-Guided Precision Conformal Ablation Therapy for Brain Tumors

描述(申请人提供)：本项目的目标是开发一种集成系统，用于MRI引导下的精确靶向和间质高强度聚焦超声(IHIFU)精确消融脑肿瘤。25%-40%的系统性癌症患者患有脑转移瘤(BM)。BMS的治疗通常是多学科的，包括开放手术、立体定向放射外科(SRS)、全脑放射治疗和/或化疗。一部分患者是开放手术和/或SRS的候选患者。在适当的患者行开颅手术，可以进行组织诊断、症状迅速缓解和局部疾病控制。SRS的优点是它是非侵入性的，避免了开颅手术相关的并发症。然而，SRS排除了组织诊断，症状缓解的时间较慢。拟议研究的目的是提供一套完整的新工具，通过不到一英寸的切口靶向和消融肿瘤，从而提供开颅手术侵入性较小的好处。因此，提供这种疗法的整套工具需要充分的可视化、精确的靶向(1 Mm)和适形消融。所提出的方法是将实时MR引导的机器人辅助的iHIFU传输与MR热成像(MRTI)反馈相结合。该系统使用与MR兼容的机器人操作器，能够提供精确度、重复性和效率所需的插管，使该疗法成为合理的辅助手段，而间质高强度超声允许进行高精度的电子可配置治疗性消融，能够以3D方式精确控制体积(大小和形状)，从非常小的(毫米)到中等(几厘米)的大小，而不会损害附近与疾病无关的关键结构。所提议的方法的意义在于它 提供了一种比开颅手术侵入性更小的选择，与SRS相比，它提供了允许组织诊断以及在人脑难以到达的区域立即切除肿瘤的优势。拟议工作的临床重点是脑转移瘤(BM)，它是坚固的，与周围组织分界良好，适合MR引导的消融。预计这种新型且高度可控的消融系统的成功开发将最终导致未来治疗其他类型的肿瘤的方法，如脑膜瘤。该项目的目标是：1)开发与MRI兼容的间质超声神经消融器；2)构建和评估用于神经消融器输送和控制的与MRI兼容的机械手；3)开发和集成基于计算机的3D治疗计划和模拟工具；4)进行临床前评估，以确认准确性，优化临床工作流程，并在临床相关环境中演示成功的消融术。该项目的成功完成将导致与一家兽医医院达成一项实验方案，将iHIFU用作治疗犬脑转移瘤的治疗范例的一部分，不久将进行人体试验。

DESCRIPTION (provided by applicant): The goal of this project is to develop an integrated system for MRI-guided precise targeting and accurate ablation of brain tumors by interstitial high intensity focused ultrasound (iHIFU). Between 25-40% of patients with systemic cancer suffer the effect of brain metastases (BM). Treatment of BMs is often multidisciplinary involving open surgery, stereotactic radiosurgery (SRS), whole brain radiation, and/or chemotherapy. A subset of patients are candidates for open surgery and/or SRS. Open surgery via craniotomy in appropriate patients allows for tissue diagnosis, rapid relief of symptoms, and local disease control. The advantage of SRS is that it is non-invasive and avoids complications associated with craniotomy. SRS, however, precludes tissue diagnosis and time to symptom relief is slower. The purpose of the proposed research is to provide a complete new set of tools offering the benefits of craniotomy less invasively by targeting and ablating tumors through an incision less than one inch. The complete set of tools to deliver this therapy thus requires adequate visualization, precise targeting (<1mm), and conformal ablation. The proposed approach is to combine real-time MR-guided robot-assisted delivery of iHIFU with MR thermal imaging (MRTI) feedback. The system uses an MR-compatible robotic manipulator capable of delivering a cannula with the accuracy, reproducibility and efficiency needed to make this therapy a reasonable adjunct, while interstitial high-intensity ultrasound allows for highly precise electronically configurable therapeutic ablation with capability for exact volume (size and shape) control in 3D, from very small (mm) to moderate (several cm) size, without harming nearby critical structures not involved with disease. The significance of the proposed approach is that it offers a less invasive alternative to craniotomy, which provides the advantage over SRS of allowing for tissue diagnosis as well as immediate tumor ablation in difficult to reach regions of the human brain. The clinical focus of the proposed work is on brain metastases (BM), which are solid, well-demarcated from surrounding tissue, and amenable to MR-guided ablations. It is anticipated that successful development of this novel and highly controllable ablation system will eventually lead to future approaches to treat other types of tumors such as meningiomas. The aims of this project are to: 1) develop a MRI-compatible interstitial ultrasonic neuroablation instrument, 2) construct and evaluate an MRI-compatible manipulator for neuroablation instrument delivery and control, 3) develop and integrate computer-based 3D treatment planning and simulation tools, and 4) perform pre-clinical evaluations to confirm accuracy, optimize clinical workflow, and demonstrate successful ablative lesioning in clinically-relevant environment. Successful completion of this project will result in an experimental protocol in place with a veterinary hospital to use iHIFU as part of a treatment paradigm for canines with brain metastases, with human studies soon to follow.