Magnetic Resonance-Guided Stereotaxy for Infusions to the Pig Brain

Jesus G. Cruz-Garza; Khaled M. Taghlabi; Lokeshwar S. Bhenderu; Shruti Gupta; Arvind Pandey; Allison M. Frazier; Shawn Brisbay; John D. Patterson; Ernesto A. Salegio; Christopher J. Kantorak; Christof Karmonik; Philip J. Horner; Robert C. Rostomily; Amir H. Faraji

doi:10.3791/64079

JoVE Journal
Neuroscience
Author Produced

This content is Free Access.

JoVE Journal Neuroscience

Magnetic Resonance-Guided Stereotaxy for Infusions to the Pig Brain

磁共振引导立体定向输注猪脑

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08:23 min

March 31, 2023

DOI: 10.3791/64079-v

Jesus G. Cruz-Garza¹, Khaled M. Taghlabi¹, Lokeshwar S. Bhenderu¹, Shruti Gupta², Arvind Pandey¹, Allison M. Frazier¹, Shawn Brisbay¹, John D. Patterson¹, Ernesto A. Salegio², Christopher J. Kantorak², Christof Karmonik³, Philip J. Horner¹, Robert C. Rostomily¹, Amir H. Faraji¹

¹Department of Neurosurgery,Houston Methodist Research Institute, ²ClearPoint Neuro, ³Translational Imaging Center,Houston Methodist Research Institute

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Overview

This study presents a protocol for performing stereotaxy on the pig brain using convection-enhanced infusions, guided by real-time magnetic resonance imaging (MRI). The aim is to demonstrate the feasibility of delivering and monitoring infusion agents in large animal models, thereby facilitating translational neurosurgical techniques.

Key Study Components

Area of Science

Neurosurgery
Magnetic Resonance Imaging
Infusion Techniques

Background

Pigs provide a valuable large animal model for neurosurgical interventions due to the size of their brains.
Real-time MRI offers guidance for precise surgical planning and infusion delivery.
The study aims to establish protocols for infusing agents effectively into the brain using advanced imaging techniques.

Purpose of Study

To demonstrate MR-guided stereotactic procedures in pigs.
To visualize infusion agent distribution in real-time.
To enable translational applications in neurosurgery.

Methods Used

The study utilizes a 3T MRI suite for imaging and guiding the stereotactic injection.
A pig model is employed for the surgical procedure, including animal positioning and securing the stereotactic frame.
Continuous monitoring of the infusion is conducted with concurrent MRI scans.
Detailed steps for the surgical procedure, including incision, drilling, and cannula insertion, are outlined.

Main Results

The protocol allows for accurate monitoring of infusion distribution in the brain through MR imaging.
Real-time adjustments in infusion parameters can be made as needed based on intraoperative imaging data.
The findings illustrate the capability of integrating imaging techniques with surgical interventions.

Conclusions

This study establishes a protocol for performing precise infusions in the pig brain using MR guidance.
The ability to monitor and adjust the infusion in real-time enhances the feasibility of drug delivery studies.
Utilizing pigs as large animal models supports advanced approaches in studying drug distribution and neurosurgical techniques.

Frequently Asked Questions

What are the advantages of using pig models for stereotactic procedures?

Pigs offer a large brain size conducive to imaging and surgical interventions, providing a more translational model for human neurosurgical applications.

How is the infusion agent distributed in the brain?

The infusion agent's distribution is monitored in real-time through concurrent MRI scans, allowing for precise evaluation of its spread within the brain tissue.

What types of imaging are used during the procedure?

Real-time magnetic resonance imaging (MRI) is employed to guide the stereotactic procedure and monitor the infusion agent's distribution.

How can this method be adapted for other interventions?

The protocol can be modified to accommodate different infusion agents or surgical techniques by adjusting the parameters based on the desired outcomes and imaging feedback.

What are some limitations of this study?

One limitation may include the need for specialized equipment and expertise in MRI guidance, which may not be readily available in all settings.

What outcomes can be measured with this approach?

This approach allows for the measurement of infusion distribution volume and real-time adjustments in infusion parameters, providing insights into drug delivery efficacy.

这里介绍的方案展示了使用对流增强输注、实时磁共振成像（MRI）可视化指导和实时输液分布可视化对猪大脑的立体定向。

在这里，我们将MR引导的立体定向定位扩展到猪脑的应用，以递送和监测输注剂的分布。猪脑的大小允许进行转化的成像和神经外科干预。我们使用猪模型在3T MRI套件中进行MR引导的立体定向注射。

我们直观地报告了猪立体定位程序的实施，并描述了MRI套件以适应猪的适应性，在视频和同步MR成像中可视化该过程以评估输注液分布。动物定位。将受试者放在MRI表中，为MRI扫描做准备。

用毛巾和泡沫垫抬高躯干。目标是头部略微向下下降，颈部弯曲，鼻子几乎接触桌子。MRI头部支架销固定在双侧颧骨上，以保持头部固定在MR工作台上。

设置后，MRI工作台被移动到扫描仪的孔中，直到受试者的头部到达孔的末端。通过 MRI 辅助可视化引导计划手术插入。以无菌方式准备该区域。

通过将网格的粘合剂侧固定在患者的头部上，以毛刺孔的位置为中心，将基准计划网格放在受试者的头皮上。在网格设置到位的情况下执行 MRI 侦察扫描。通过在软件中手动拖动投影的入口点和目标点来调整建议的轨迹，包括所需的入口点和目标点，以避免血管并最大限度地减少剥离和沟违规。

根据外科医生的偏好确定所需的轨迹后，运行MR引导软件以找到网格上的入口点。固定立体定向框架并通过软件投影迭代调整对齐方式。首先用六个骨锚螺钉和四个偏置螺钉固定底座，围绕网格上所需的入口点坐标组装立体定向框架。

将六个骨锚螺钉固定在头骨上，通过头皮通过网格。六个锚固螺钉用于稳定立体定向框架并避免钻孔过程中的任何移动。通过固定在头骨上的皮肤固定位于塔底部的四个偏置螺钉。

它们起到反作用力，通过将框架底座提升到中心螺钉上来拧紧中心骨螺钉并稳定底座。立体定向框架底座固定后，继续框架组装。执行高分辨率、T1 加权、MP-RAGE MRI 扫描，这是 MRI 软件中的一个选项，并设置框架以捕获帧基准点并确认轨迹。

使用软件确认所需的投影套管插入轨迹。通过转动指轮执行俯仰、横滚和 XY 调整，如软件中的输出调整参数所示。使用MR引导软件，测量所需轨迹的头骨厚度和到大脑的总距离。

钻孔并插入套管进行输液。在进行切口之前使用碘磨砂膏以防止感染。在立体定向框架下使用手术刀在头皮上做一个三厘米的切口。

通过在创建检修孔之前执行调整来设置钻孔插入框架。拆下中心导向管并将其更换为适合钻孔的 3.4 毫米钻头的导向管。确保助手在场以将框架固定到位，同时外科医生使用手动钻头进行钻头，以增加框架的额外稳定性。

为第二个钻头插入设置框架，以加宽毛刺孔并避免可能改变轨迹的骨质碰撞。使用 4.5 毫米钻头设置钻头。将中心导轨更换为适合此较大钻头的导轨。

创建一个 4.5 毫米的毛刺孔。用锋利的探针刺穿硬脑膜。插入预先灌注的、与框架兼容的输液插管。

请确保套管具有一致的中性或正背压，以消除引入的气泡。该软件为计划目标提供特定的深度。测量立体定向框架兼容输液插管的深度，并使用与套管相关的深度停止。

通过重复MRI扫描监测输液。开始输注所需药物，与钆造影剂共同输注。定期进行MRI扫描，以监测脑中插管剂的输注和分布量，这可以由于钆的共同输注而推断。

套管尖端周围的高信号区域表明存在钆基造影剂。输注结束后，停止泵。在取出套管之前，让套管在输注终止后在大脑中停留五分钟。

MRI扫描仪中的猪位置为外科医生提供了最佳的手术通道，并为立体定向框架和输液插管提供了间隙。MRI引导的可视化允许精确规划和插入大脑套管。立体定向框架在软件中扫描，并进行调整以有效地到达所需位置。

套管输注后的反复术间MRI扫描显示输液如何输送到脑组织。立体定向框架允许精确和受控地注入猪脑模型。通过该协议，我们确定输注速率或套管插入的准确性等参数可以实时更改或根据术中成像的要求暂停。

实时MR成像系统可以准确确定分布体积。猪作为实时MRI跟踪输液的大型动物模型，提供了研究通过细胞递送和其他具有翻译价值的药物向大脑输送药物的可能性。MR 引导的可视化为进入猪脑、插入套管和监测输液剂提供实时指导。

据报道，钻孔过程、组织变形和/或白质束中断会导致困难和药物输送到大脑。计划期间的迭代MRI扫描和套管插入提供了小调整的能力。

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