Name: a mri-based toolbox for neurosurgical planning in nonhuman primates
Uploaded: 2020-07-17T14:00:00
Description: Watch this Scientific Journal Video about A MRI-Based Toolbox for Neurosurgical Planning in Nonhuman Primates at JoVE.com

该项目得到了国家卫生研究院尤尼斯·肯尼迪·希弗国家儿童健康与人类发展研究所（K12HD073945奖）、华盛顿国家灵长类动物研究中心（WaNPCR、P51 OD010425）、神经技术中心（CNT、授予EEC-1028725下的国家科学基金会工程研究中心）和华盛顿大学版税研究基金的支持。为该项目向麦克尼克和马丁内斯-康德实验室提供的资金来自大脑倡议 NSF-NCS 奖 1734887，以及 NSF 奖 1523614 和 1829474，以及 SUNY 帝国创新者奖学金。该奖学金授予每位教授。我们感谢卡拉姆·哈提布在阿加罗斯准备方面的帮助，感谢托尼·朱恩的技术支持。

所有动物程序都得到华盛顿大学动物护理和使用研究所委员会的批准。使用了两只雄性恒河猴（猴子H：14.9公斤和7岁，猴子L：14.8公斤和6岁）。
1. 图像采集
<ol><li>将猴子运送到3T MRI扫描仪，将动物放在一个与MRI兼容的立体轴框（材料表）。</li>
	<li>记录标准T1（翻转角度 = 8°，重复时间/回声时间 = 7.5/3.69 s，矩阵大小 = 432 x 432 x 80，采集持续时间 = 103.7 s，多可可?...

<ol>
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本文介绍了一个工具箱，用于准备神经保险在NHPs使用物理和CAD模型的头骨和大脑解剖从 MR扫描提取。
虽然提取和3D打印的头骨和大脑模型是专门为准备颅骨切除术和头部后植入而设计的，但这种方法适用于其他几个应用。如前所述，头骨的物理模型允许在手术前预弯曲头部后，从而与头骨形成良好的配合。此外，从MRI提取的头骨可用于生成一个3D设计的后柱，对头骨解剖具有...

灵长类动物研究是医学研究从动物模型到人体试验1、2的关键一步。这在神经科学和神经工程研究中尤为如此，因为啮齿动物的大脑与非人类灵长类动物的大脑（NHP）1、2、3之间存在巨大的生理和解剖学差异。随着化学遗传学、光遗传学和钙成像等新兴基因技术需要神经元进行基因改造，研究NHP神经功能的神经工程研究作为理解大脑功能2、4、5、6、7、8、9、10、11、12、13、14、15、16的临床前模型得到了特别关注。在大多数NHP神经科学实验中，需要神经外科措施来植入各种设备，如头部柱、刺激和记录室、电极阵列和光学窗口4、5、6、7、10、11、13、14、15、17、18。
目前的NHP实验室使用各种方法，通常包括无效的做法，包括对动物进行窒息，以适合头部柱的腿，并近似颅骨切除地点周围的头骨曲率。其他实验室在手术中将头部柱贴到头骨上，或采用更先进的方法获得必要的植入测量，如分析NHP脑图集和磁共振（MR）扫描，试图估计头骨曲率2，10，11，16。NHPs中的神经外科医生也涉及液体注射，实验室通常无法仅依靠立体测量和与 MR 扫描进行比较，才能将大脑 2、4、5、13、14内的预计注射位置可视化。这些方法有一定程度的不可避免的不确定性，无法测试植入物的所有复杂组件的物理兼容性。
因此，需要一种精确的非侵入性方法来进行NHPS的神经外科规划。在这里，我们提出了一个协议和方法，准备植入和注射手术在这些动物。整个过程源于MRI扫描，从数据中提取大脑和头骨，创建三维（3D）模型，然后可以3D打印。头骨和大脑模型可以结合，以准备颅骨切除术以及头部柱与提高的准确性水平。大脑模型还可用于创建用于铸造大脑解剖上准确的凝胶模型的模具。凝胶大脑单独和结合提取的头骨可用于准备各种注射手术。下面我们将介绍基于 MRI 的神经外科准备工具箱所需的每个步骤。

<table>
	<tbody>
		<tr>
			<td>3D Printing Software (GrabCAD Print)</td>
			<td>Stratasys</td>
			<td>Version 1.36</td>
			<td>Used for High quality 3D printing</td>
		</tr>
		<tr>
			<td>3D Printing Software (Simplify 3D)</td>
			<td>Simplify3D</td>
			<td>Version 4.1</td>
			<td>Used for PLA 3D printing</td>
		</tr>
		<tr>
			<td>Agarose</td>
			<td>Benchmark Scientific</td>
			<td>A1700</td>
			<td>Used for making gel brains</td>
		</tr>
		<tr>
			<td>Black Nail Polish</td>
			<td>L.A. Colors</td>
			<td>CNP637</td>
			<td>Used for gel molding</td>
		</tr>
		<tr>
			<td>Cannula (ID 320 um, OD 432 um)</td>
			<td>Polymicro Technologies</td>
			<td>1068150627</td>
			<td>Used to inject dye into gel brain</td>
		</tr>
		<tr>
			<td>Cannula (ID 450 um, OD 666 um)</td>
			<td>Polymicro Technologies</td>
			<td>1068150625</td>
			<td>Used to inject dye into gel brain</td>
		</tr>
		<tr>
			<td>Catheter Connector</td>
			<td>B Braun</td>
			<td>PCC2000</td>
			<td>Perifix for 20-24 Gage epidural catheters; Units per Cs 50</td>
		</tr>
		<tr>
			<td>Dremel 3D Digilab 3D45 printer</td>
			<td>Dremel</td>
			<td>F0133D45AA</td>
			<td>Used for prototyping in PLA</td>
		</tr>
		<tr>
			<td>ECOWORKS</td>
			<td>Stratasys</td>
			<td>300-00104</td>
			<td>Used to dissolve QSR support structures</td>
		</tr>
		<tr>
			<td>Erlymeyer flask</td>
			<td>Pyrex</td>
			<td>4980</td>
			<td>Used for gel molding</td>
		</tr>
		<tr>
			<td>Ethyl cyanoacrylate</td>
			<td>The Original Super Glue Corp.</td>
			<td>15187</td>
			<td>Used to make combined cannula</td>
		</tr>
		<tr>
			<td>Graduated cylinder</td>
			<td></td>
			<td>3023</td>
			<td>Used for gel molding</td>
		</tr>
		<tr>
			<td>HATCHBOX PLA 3D Printer Filament</td>
			<td>HATCHBOX</td>
			<td>3DPLA-1KG1.75-RED/3DPLA-1KG1.75-BLACK</td>
			<td>1kg Spool, 1.75mm, Red/Black</td>
		</tr>
		<tr>
			<td>Locust Bean Gum</td>
			<td>Modernist Pantry</td>
			<td>1018</td>
			<td>Gumming agent for gel brain mixtures</td>
		</tr>
		<tr>
			<td>MATLAB</td>
			<td>MathWorks</td>
			<td>R2019b</td>
			<td>Used for skull extraction</td>
		</tr>
		<tr>
			<td>McCormick Yellow Food Color</td>
			<td>McCormick</td>
			<td></td>
			<td>Used for dye injection</td>
		</tr>
		<tr>
			<td>Microwave</td>
			<td>Panasonic</td>
			<td>NN-SD975S</td>
			<td>Used for agarose curing</td>
		</tr>
		<tr>
			<td>MR Imaging Software (3D Slicer)</td>
			<td>3D Slicer</td>
			<td>Version 4.10.2</td>
			<td>Used for 3D model generation</td>
		</tr>
		<tr>
			<td>MR Imaging Software (Mango with BET plugin)</td>
			<td>Reasearch Imaging Institute</td>
			<td>Version 4.1</td>
			<td>Used for brain extraction</td>
		</tr>
		<tr>
			<td>Philips Acheiva MRI System</td>
			<td>Philips</td>
			<td>4522 991 19391</td>
			<td>Used to image non-human primates</td>
		</tr>
		<tr>
			<td>Phosphate Buffered Solution</td>
			<td>Gibco</td>
			<td>70011-044</td>
			<td>10X diluted with DI water to 1X</td>
		</tr>
		<tr>
			<td>Pump</td>
			<td>WPI</td>
			<td>UMP3T-1</td>
			<td>Used for dye injection</td>
		</tr>
		<tr>
			<td>Pump driver</td>
			<td>WPI</td>
			<td>UMP3T-1</td>
			<td>Used for dye injection</td>
		</tr>
		<tr>
			<td>Refrigerator</td>
			<td>General Electric</td>
			<td></td>
			<td>Used to preserve agarose gel</td>
		</tr>
		<tr>
			<td>Scientific Spatula</td>
			<td>VWR</td>
			<td>82027-494</td>
			<td>Used to extract gel molds</td>
		</tr>
		<tr>
			<td>SolidWorks</td>
			<td>Dassault Systemes</td>
			<td>2019</td>
			<td></td>
		</tr>
		<tr>
			<td>Stratasys ABS-M30 filament</td>
			<td>Stratasys</td>
			<td>333-60304</td>
			<td>Used for high quality 3D printing</td>
		</tr>
		<tr>
			<td>Stratasys F170 3D printer</td>
			<td>Stratasys</td>
			<td>123-10000</td>
			<td>Used for high quality 3D printing</td>
		</tr>
		<tr>
			<td>Stratasys QSR support</td>
			<td>Stratasys</td>
			<td>333-63500</td>
			<td>Used to create supports with ABS model</td>
		</tr>
		<tr>
			<td>Syringe</td>
			<td>SGE</td>
			<td>SGE250TLL</td>
			<td>Used for dye injection</td>
		</tr>
	</tbody>
</table>

a mri-based toolbox for neurosurgical planning in nonhuman primates

在这篇论文中，我们概述了一种手术制备方法，该方法仅使用从磁共振成像 （MRI） 中提取的数据对 NHP 中的各种神经外科医生进行实际规划。该协议允许生成3D打印解剖上准确的大脑和头骨的物理模型，以及大脑建模一些机械特性的阿加罗斯凝胶模型。这些模型可以从MRI中提取，使用大脑模型的大脑提取软件，以及头骨模型的自定义代码。制备方案利用最先进的3D打印技术，为凝胶大脑模型制作连接大脑、头骨和模具。头骨和大脑模型可用于可视化颅内脑组织，并在自定义代码中添加颅骨切除术，从而更好地为直接涉及大脑的手术做准备。这些方法的应用是专为神经刺激和记录以及注射手术而设计的，但该系统的多功能性允许将来将协议、提取技术和模型扩展至更广泛的手术范围。

过去2、5、10、16年，MRIS作为术前颅骨切除术规划措施的操纵和分析已成功使用。然而，由于增加了大脑、头骨和颅骨的3D建模，这个过程得到了极大的加强。我们能够成功地创建一个分析上准确的大脑物理模型，反映我们研究的兴趣领域（图1）。同样，我们能够从 MR 图像中提?...

Watch this Scientific Journal Video about A MRI-Based Toolbox for Neurosurgical Planning in Nonhuman Primates at JoVE.com

A MRI-Based Toolbox for Neurosurgical Planning in Nonhuman Primates

下面概述的方法旨在提供一个全面的方案，准备非人类灵长类动物（NHP）神经外科使用三维（3D）打印方法和MRI数据提取的新组合。

非人类灵长类动物神经外科规划基于MRI的工具箱

In this paper, we outline a method for surgical preparation that allows for the practical planning of a variety of neurosurgeries in NHPs solely using ...

该协议对神经工程领域意义重大，因为它提供了一个简洁和单模程序，旨在提高非人类灵长类动物神经外科的精度和安全性。这项技术为研究人员提供了独特的能力，可以可视化他们的植入或注射过程的各个方面，并确保他们可以尽可能进入手术室准备。此方法的可视化演示至关重要，因为它突出了生命大小的物理模型对手术规划的影响和清晰度。要在磁共振成像软件中提取大脑，请打开插件下拉菜单并选择提取大脑。将提取强度阈值设置为 2.5、2.7，将阈值梯度值设置为零。创建大脑图像的位图后，选择图像菜单下的生成曲面，并输入用于创建包含感兴趣区域的位图的阈值。然后单击"确定"以创建曲面。并保存提取的大脑区域感兴趣作为NII或NII。GZ 文件。要生成大脑模型，请打开适当的医学图像处理软件中提取的大脑文件。在编辑器模块菜单中，选择阈值效果，调整阈值范围滑块，以便包含大脑的位图部分在所有三个切片中突出显示。打开模型制造商模块，并在输入卷下拉菜单中，选择位图文件。在"模型"下，选择"创建新模型层次结构"，然后单击"应用"以创建卷。导入的网状大脑表面导入后，选择图形 1。并禁止任何不必要的图形功能，直到只有包含大脑的特征留在文件中。然后，将文件保存在 PRT 格式中，以进行进一步操作，并保存为用于 3D 打印的 STL。对于大脑成型，将提取的大脑模型加载到适当的计算机设计软件程序中。在插入菜单的特征部分下，选择转换为网格体和大脑的图形体以将其转换，然后打开此草图选项卡并单击草图以选择顶部平面作为草图平面。围绕感兴趣的整个半球绘制一个矩形，并选择拉伸凸台基特征以拉伸包含大脑顶部的立方矩形。在"插入"菜单的"要素"部分下，选择"转换为网格实体"，然后选择实体文件夹中的拉伸立方体以进行转换。要创建负空间，请使用组合特征并选择减法选项从新拉伸的多维块中减去大脑模型。对于头骨建模，将快速 MPRAGE MRI 导入适当的矩阵操作软件程序作为 DICOM 文件。并尽可能使用命令将所有帧合并到单个 3D 矩阵中。确保矩阵的每个 2D 帧显示一个日冕切片，并使用大于运算符的单个像素值来阈值 3D 矩阵以创建二进制掩码。然后调整阈值，使头骨解剖被面罩捕获。要移除肌肉图层，请从蒙版中迭代抓取 2D 切片，以分别处理 3D 蒙版中每个帧，并使用波浪线运算符反转蒙版的值。头骨值将是一个。外部和大脑的值为零。向 3D 蒙版添加额外的空体素，直到蒙版的最低分辨率尺寸大于比例因子定义的因子。并在蒙版中线性插值，直到蒙版填充新空间。然后，将头骨导出为 STL 文件或用于 3D 打印的类似文件类型。若要在 3D 头骨模型中创建颅骨切除术，请打开 MRI 文件，然后手动扫描 3D 矩阵，使用猴子大脑图集中的解剖地标确定颅骨切除术的大致位置。要创建一个阿加罗斯模具，将阿加罗斯溶液倒入一个完整的或半半球脑模中，让溶液在模具内凝固约两个小时。当 agarose 已设置时，使用铲子轻轻地从模具中取出凝胶模型，注意，不要损坏模具表面。对于 agarose 凝胶模型的模拟注入，将注射器泵安装在立体税架上的立体轴上，然后用电离水填充 250 微升注射器。将注射器装到注射器泵上，并完全将注射液充满水。使用泵驱动器将食物着色的目标体积加载到注射器中进行注射。弹出食物色素，直到在菜角尖形成一个小珠子。从管尖干燥珠子，将凝胶模型定位在管下。降低管，直到尖端接触凝胶模型的表面，并注意立体税臂上的测量结果。然后平稳、快速地将管切成凝胶模型，以达到目标注射深度。确保凝胶表面密封在管周围并运行泵，同时观察模具的扩散，直到目标体积已交付。利用这个协议，可以创建非人类灵长类大脑的解剖学上精确的物理模型。同样，也可以生成从磁共振图像中提取的灵长类头骨的解剖学上精确的物理模型。头骨和大脑的物理模型可以与紧密干扰配合相结合，验证两个模型相对于彼此的准确性，并使外推的MRI分析数据合法化。在打印前将颅骨切除术插入头骨，可以组合样品界面的所有部分，以评估与头骨和大脑相关的各种成分的几何形状。例如，在此实验中，在手术前，头部柱的脚纵并安装到植入位置的头骨曲率上。使手术时间从开到植入约2.5小时缩短到1小时，大大降低了手术并发症的风险。阿加罗斯混合脑模型可以在感兴趣的区域注射黄色染料，以估计建议的输液量，并结合阿加罗斯模型与3D打印头骨可用于建模病毒载体注射手术。考虑到不同动物头骨和大脑解剖的变化，在提取过程中的成功将需要在迭代步骤中进行调整。因此，这个工具箱可以用来降低非人类灵长类神经外科的风险，制造技术可以增强神经科学前沿的实验过程。

Research

JoVE Journal

Bioengineering

A Method for Ovarian Follicle Encapsulation and Culture in a Proteolytically Degradable 3 Dimensional System

卵泡在蛋白质降解的3维系统的封装和文化的一种方法

The ovarian follicle is the functional unit of the ovary that secretes sex hormones and supports oocyte maturation. In vitro  follicle techniques provide ...

科研

生物工程

Fabrication of Electrochemical-DNA Biosensors for the Reagentless Detection of Nucleic Acids, Proteins and Small Molecules

无试剂检测核酸，蛋白质和小分子的电化学DNA生物传感器的制备

As medicine is currently practiced, doctors send specimens to a central laboratory for testing and thus must wait hours or days to 
receive the results. ...

Creating Two-Dimensional Patterned Substrates for Protein and Cell Confinement

蛋白质和细胞坐月子创建二维图案衬底

Microcontact printing provides a rapid, highly reproducible method for the creation of well-defined patterned substrates.1  While microcontact printing ...

Adaptation of a Haptic Robot in a 3T fMRI

触觉机器人适应在3T功能磁共振成像

Functional magnetic resonance imaging (fMRI) provides excellent functional brain imaging via the BOLD signal 1 with advantages including non-ionizing ...

Cellular Lipid Extraction for Targeted Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry Analysis

有针对性的稳定同位素稀释液相色谱 - 质谱法分析细胞脂质提取

The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including ...

Nonhuman Primate Lung Decellularization and Recellularization Using a Specialized Large-organ Bioreactor

非人灵长类龙脱细胞和Recellularization使用专门的大型器官生物反应器

There are an insufficient number of lungs available to meet current and future organ transplantation needs. Bioartificial tissue regeneration is an ...

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

用化学表观修饰因子重定向细胞机械抑制基因转录

Regulation of chromatin compaction is an important process that governs gene expression in higher eukaryotes. Although chromatin compaction and gene ...

In Silico Modeling Method for Computational Aquatic Toxicology of Endocrine Disruptors: A Software-Based Approach Using QSAR Toolbox

在内分泌干扰物计算水生毒理学的Silico建模方法：使用QSAR工具箱的基于软件的方法

Computational analyses of toxicological processes enables high-throughput screening of chemical substances and prediction of their endpoints in biological ...

A Human 3D Extracellular Matrix-Adipocyte Culture Model for Studying Matrix-Cell Metabolic Crosstalk

用于研究基质细胞代谢串扰的人类3D细胞外基质-脂肪培养模型

The extracellular matrix (ECM) plays a central role in regulating tissue homeostasis, engaging in crosstalk with cells and regulating multiple aspects of ...

Patient-Specific Polyvinyl Alcohol Phantom Fabrication with Ultrasound and X-Ray Contrast for Brain Tumor Surgery Planning

患者特异性聚乙烯酒精幻影制造与超声波和X射线对比脑肿瘤手术规划

Phantoms are essential tools for clinical training, surgical planning and the development of novel medical devices. However, it is challenging to create ...