Platform for MR-Guided Neurotherapeutic Drug Delivery

MR 引导神经治疗药物输送平台

• 批准号: 8648801
• 负责人: Edward Ray Barker
• 金额: $ 21.62万
• 依托单位: INSERT, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-27 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648801
• 关键词: Address; Adoption; Algorithms; Animal Model; Biopsy; Blood - brain barrier anatomy; Brain; Brain imaging; Bypass; Cadaver; Cannulas; Catheters; Characteristics; Clinical; Computer Interface; Computer software; Convection; Data; Data Set; Dependency; Development; Devices; Disease; Dose; Drug Delivery Systems; Drug Monitoring; Effectiveness; Encapsulated; Evaluation; FDA approved; Family suidae; Foundations; Funding; Gene Delivery; Goals; Head; Human; Image; Imagery; Imaging Device; Imaging Techniques; Imaging technology; Implant; Infusion procedures; Injection of therapeutic agent; Kinetics; Lead; Lesion; Location; Magnetic Resonance Imaging; Manufacturer Name; Marketing; Measures; Mental disorders; Methods; Modeling; Monitor; Neurosurgeon; Neurosurgical Procedures; Operative Surgical Procedures; Outcome; Parkinson Disease; Patients; Pharmaceutical Preparations; Phase; Physics; Physiologic pulse; Plague; Positioning Attribute; Prevalence; Procedures; Research; Research Personnel; Safety; Scanning; Small Business Innovation Research Grant; Solutions; Specificity; Speed; Surgeon; System; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Training; Universities; Wisconsin; base; brain surgery; brain tissue; coronal suture; design; drug distribution; experience; gene therapy; image reconstruction; in vivo; innovation; monitoring device; neurosurgery; operation; patient safety; platform-independent; preclinical study; prospective; prototype; public health relevance; tool

Significance: Accurate targeting, guidance and monitoring of interventional therapy in the brain are critical for maximizing the effectiveness and safety during and following neurosurgical procedures. Magnetic resonance imaging (MRI) is a critical tool for planning and guiding neurosurgical procedures. In most cases, the MRI is obtained during a pre-operative session; however, either brain shift, errors in device guidance or device malfunction can lead to poor outcomes. In particular for infusion-based therapies, the location of the infusion cannula in the brain, the distribution of the therapeutic agent, and loss of the therapeutic agent through backflow or other mechanisms may significantly influence the therapeutic outcome. While luminaries have shown how intraoperative MRI can visualize infusion distribution qualitatively, neurosurgeons will largely resist MRI's complicated workflow, lack of interactive feel, and inability to interface with the surgical workstations they commonly utilize to exploit imaging. Hypothesis: We hypothesize that by decoupling imaging control from MR scanner manufacturers, we can produce an encapsulated, real-time MRI platform technology, in this case designed for guiding and monitoring drug infusions. The customizable platform, ultimately designed and controlled by our device and surgical workstation partners, will reduce the time of MR-guided targeting, quantitatively visualize the current infusion in real-time, and provide an intuitive, interactive workflow familiar to surgeons. Preliminary Data: We have developed a prototype platform for real-time, interactive navigation of cannulas into the brain and the imaging technology to quantitatively measure infusion distribution. We have successfully applied the platform to guide 30 convection enhanced delivery procedures in in-vivo swine brains and one gene delivery in a NHP model. Specific Aims: This project includes further development and evaluation of the platform for navigation and monitoring of neuroinfusion procedures. In Specific Aim 1, we will simplify and accelerate the interface platform for guiding and monitoring infusion procedures. We will integrate new imaging tools into the platform for obtaining the roadmap image for targeting and imaging sequences for monitoring the infusion distribution. In Specific Aim 2, we will demonstrate that entire platform for navigation and infusion monitoring under the guidance of a newly trained neurosurgeon using a cadaver brain model. Navigation time for device alignment and insertion will be reduced to under 10 minutes. The platform will also be tested in guiding a gene delivery treatment in three in-vivo NHP models. The successful completion of this project will result in a comprehensive, integrated platform for clinically effective image-guided infusion therapies in the human brain.

意义：脑部介入治疗的准确定位、指导和监测对于 最大限度地提高神经外科手术期间和之后的有效性和安全性。磁共振 成像 (MRI) 是规划和指导神经外科手术的重要工具。在大多数情况下，MRI 是 在术前会议期间获得；然而，要么大脑转移，要么设备引导错误，要么设备 故障可能会导致不良结果。特别是对于基于输注的治疗，输注的位置 大脑中的插管、治疗剂的分布以及治疗剂的损失 回流或其他机制可能会显着影响治疗结果。虽然发光体有 显示了术中 MRI 如何定性地可视化输注分布，神经外科医生将在很大程度上抵制 MRI 的工作流程复杂、缺乏交互感、无法与手术工作站交互 通常用于开发成像。假设：我们假设通过将成像控制与 MR 解耦 扫描仪制造商，我们可以生产封装的实时 MRI 平台技术，在这种情况下 设计用于指导和监测药物输注。最终设计和定制的可定制平台 由我们的设备和手术工作站合作伙伴控制，将减少 MR 引导定位的时间， 实时定量可视化当前输液，并提供熟悉的直观、交互式工作流程 外科医生。初步数据：我们开发了一个原型平台，用于实时交互式导航 将插管插入大脑并利用成像技术定量测量输液分布。我们有 成功应用该平台指导30例猪体内对流增强递送程序 以及 NHP 模型中的一种基因传递。具体目标：该项目包括进一步开发和 评估神经输注程序导航和监测平台。在具体目标 1 中，我们将 简化并加速用于指导和监控输液程序的接口平台。我们将整合 平台中引入了新的成像工具，用于获取目标定位的路线图图像和成像序列 监测输液分布。在具体目标 2 中，我们将演示整个导航平台 以及在新训练的神经外科医生的指导下使用尸体大脑模型进行输液监测。 设备对齐和插入的导航时间将减少到 10 分钟以下。该平台还将 在三个体内 NHP 模型中进行指导基因递送治疗的测试。本次活动的顺利完成 该项目将打造一个全面、集成的平台，用于临床有效的图像引导输注 人脑疗法。