Name: image-guided convection-enhanced delivery into agarose gel models of the brain
Uploaded: 2014-05-14T13:45:00
Description: Watch this Scientific Journal Video about Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain at JoVE.com

笔者想从磁共振成像设备在塞姆斯 - 墨菲诊所，孟菲斯，田纳西州以及神经外科部门田纳西大学健康科学中心在孟菲斯大学，田纳西感谢工作人员。

凝胶幻影1。制备及染料<ol><li>通过以1,000 ml去离子水将2克0.1％的琼脂糖粉制备0.2％琼脂糖凝胶上。搅拌约1分钟，将溶液以保证适当的混合;并立即微波解决方案，在3分钟的间隔为9分钟，或直至清晰，间隔之间搅拌。 </li><li>而琼脂糖凝胶是液体，将溶液倒入5厘米×5厘米×5厘米的容器中。允许空间在容器的顶部，以加水，并允许琼脂糖凝胶冷却并沉降。 </li><li>一旦琼脂糖凝胶凝固后（约1-2小时）?...

<ol>
	<li>Miranpuri, G. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene-based+therapy+of+Parkinson's+Disease:+Translation+from+animal+model+to+human+clinical+trial+employing+convection+enhanced+delivery.">Gene-based therapy of Parkinson's Disease: Translation from animal model to human clinical trial employing convection enhanced delivery.</a> Annals of Neurosciences. 19, 133-146 (2012).</li><li>Sillay, K., Hinchman, A., Akture, E., Salamat, S., Miranpuri, G., Williams, J., Berndt, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection+Enhanced+Delivery+to+the+Brain:+Preparing+for+Gene+Therapy+and+Protein+Delivery+to+the+Brain+for+Functional+and+Restorative+Neurosurgery+by+Understanding+Low-Flow+Neurocatheter+Infusions+Using+the+Alaris&#174;+System+Infusion+Pump.">Convection Enhanced Delivery to the Brain: Preparing for Gene Therapy and Protein Delivery to the Brain for Functional and Restorative Neurosurgery by Understanding Low-Flow Neurocatheter Infusions Using the Alaris&#174; System Infusion Pump.</a> Annals of Neurosciences. 20, (2013).</li><li>Song, D. 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T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convective+distribution+of+macromolecules+in+the+primate+brain+demonstrated+using+computerized+tomography+and+magnetic+resonance+imaging.">Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging.</a> Journal of neurosurgery. 98, 584-590 (2003).</li><li>Lonser, R. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+and+safe+perfusion+of+the+primate+brainstem:+in+vivo+magnetic+resonance+imaging+of+macromolecular+distribution+during+infusion.">Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion.</a> Journal of neurosurgery. 97, 905-913 (2002).</li><li>Raghavan, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection-enhanced+delivery+of+therapeutics+for+brain+disease,+and+its+optimization.">Convection-enhanced delivery of therapeutics for brain disease, and its optimization.</a> Neurosurg Focus. 20, (2006).</li><li>Sillay, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Benchmarking+the+ERG+valve+tip+and+MRI+Interventions+Smart+Flow+neurocatheter+convection-enhanced+delivery+system's+performance+in+a+gel+model+of+the+brain:+employing+infusion+protocols+proposed+for+gene+therapy+for+Parkinson's+disease.">Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease.</a> Journal of neural engineering. 9, (2012).</li><li>Schomberg, D., Wang, A., Marshall, H., Sillay, K., Miranpuri, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ramped-Rate+vs.+continuous+rate+infusions:+An+in+vitro+comparison+of+Convection+Enhanced+Delivery+protocols.">Ramped-Rate vs. continuous rate infusions: An in vitro comparison of Convection Enhanced Delivery protocols.</a> Annals of Neurosciences. 20, (2013).</li><li>Sillay, K. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perioperative+Brain+Shift+and+Deep+Brain+Stimulating+Electrode+Deformation+Analysis:+Implications+for+rigid+and+non-rigid+devices.">Perioperative Brain Shift and Deep Brain Stimulating Electrode Deformation Analysis: Implications for rigid and non-rigid devices.</a> Ann Biomed Eng. 41, 293-304 (2013).</li><li>Brodsky, E., Block, W., Alexander, A., Emborg, M., Ross, C., Sillay, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+Device+Targeting+using+Real-Time+MRI.">Intraoperative Device Targeting using Real-Time MRI.</a> Biomedical Sciences and Engineering Conference, BSEC. , (2011).</li><li>Sillay, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strategies+for+the+delivery+of+multiple+collinear+infusion+clouds+in+convection-enhanced+delivery+in+the+treatment+of+Parkinson's+disease.">Strategies for the delivery of multiple collinear infusion clouds in convection-enhanced delivery in the treatment of Parkinson's disease.</a> Stereotactic and functional neurosurgery. 91, 153-161 (2013).</li><li>Brady, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathways+of+infusate+loss+during+convection-enhanced+delivery+into+the+putamen+nucleus.">Pathways of infusate loss during convection-enhanced delivery into the putamen nucleus.</a> Stereotactic and functional neurosurgery. 91, 69-78 (2013).</li><li>White, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+evaluation+of+the+relationships+between+catheter+design+and+tissue+mechanics+in+achieving+high-flow+convection-enhanced+delivery.">An evaluation of the relationships between catheter design and tissue mechanics in achieving high-flow convection-enhanced delivery.</a> J Neurosci Methods. 199, 87-97 (2011).</li><li>Fiandaca, M. S., Forsayeth, J. R., Dickinson, P. J., Bankiewicz, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+convection-enhanced+delivery+platform+in+the+treatment+of+neurological+diseases.">Image-guided convection-enhanced delivery platform in the treatment of neurological diseases.</a> Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 5, 123-127 (2008).</li><li>Jagannathan, J., Walbridge, S., Butman, J. A., Oldfield, E. H., Lonser, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+ependymal+and+pial+surfaces+on+convection-enhanced+delivery.">Effect of ependymal and pial surfaces on convection-enhanced delivery.</a> Journal of neurosurgery. 109, 547-552 (2008).</li><li>Chen, Z. J., Broaddus, W. C., Viswanathan, R. R., Raghavan, R., Gillies, G. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraparenchymal+drug+delivery+via+positive-pressure+infusion:+experimental+and+modeling+studies+of+poroelasticity+in+brain+phantom+gels.">Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels.</a> IEEE transactions on bio-medical engineering. 49, 85-96 (2002).</li><li>Chen, Z. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+realistic+brain+tissue+phantom+for+intraparenchymal+infusion+studies.">A realistic brain tissue phantom for intraparenchymal infusion studies.</a> Journal of neurosurgery. 101, 314-322 (2004).</li><li>Richardson, R. 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H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+utility+of+a+patient-specific+algorithm+for+simulating+intracerebral+drug+infusions.">Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.</a> Neuro-oncology. 9, 343-353 (2007).</li></ol>

<html>为确保输液成功的关键步骤是：吹扫气的输液管，混合琼脂糖凝胶，分析的MR数据，使用小的内导管的直径，使用阶梯导管设计，以减少回流，并最小化所感受到的压力凝胶或组织到其中的药物被注入。如前所述，主要损害输液的成功是输液管的空气。正确地和彻底吹扫空气的输液管是至关重要的，以确保没有空气进入输液。同样重要的是混合的琼脂糖凝胶电泳图谱。不当合成的凝胶可能导?...

对流增强输送（CED）已被提议作为用于神经病症包括恶性脑瘤，癫痫，代谢疾病，神经变性疾病（如帕金森病）1，中风和创伤2的广谱治疗选择。 CED采用正压主体流动的药物或其它输注液的分布。 CED提供安全，可靠，且均匀交付分子量化合物，从低到高，在临床相关卷3。传统的药物递送到脑组织受到严重的血-脑屏障4的限制。由内皮细胞间的紧密连接构成的毛细血管在大脑中，血 - 脑屏障块极性和高分子量的分子进入大脑实质内形成。通过海关直接实质内脑灌注可以克服以前的治疗药物传递方式的局限性并允许使用的治疗剂，不会穿过血-脑屏障，因此，此前已作为可行的治疗方案5不可用。 从健康的美国国立卫生研究院（NIH）的研究人员描述土木工程署在上世纪90年代初，作为实现更大的治疗药物浓度的方法比单纯扩散6-8。 CED的第一方法涉及植入一个或多个导管进入大脑，连接输液泵的导管，并直接泵送治疗剂进入目标区域。增加的分布分数和相对稳定的浓度被报道发生如由输液泵产生的正压引起的组织扩张，并允许该药物9的渗透。 最根本的技术CED在很大程度上仍然是它第一次描述的相同。在导管设计10，输液技术进展<su对&gt; 11，管路压力监测2，并实时MRI监测来纠正脑移位12，13，优化多个共线输注14，并监测输液损失15都增加了治疗10的安全性和有效性。额外的重要性已经被放置在导管的设计和输注策略，包括流速。成功的CED，用有限的导管回流和组织损伤，已与相关导管设计和输注速度。使用的导管的具有窄的直径和低输注率，以限制沿脑导管接口倒流以及损坏限制在导管末端16。磁共振成像提供了正确的位置，输液导管置入的视觉确认，因而给药，同时还允许修正输液回流或异常分娩17。 MR图像，也可以用于近似和跟踪分配的体积（VD输注的药物）。在VD是使 ​​用磁共振成像信号强度值大于上述平均值与周围非灌注胶为18分割阈值三个标准差来计算。在Vd为CED为一种有用的测量，因为它代表分布在大脑中的药物的体积。随着输注（六）音量，比率可以生成（VD / VI）量化所涵盖的输注药物的体积。 琼脂糖凝胶体模模仿人类大脑的理解CED等重要几个关键的机械性能：VD，凝胶导管相互作用，多孔弹性性能，并输注云形态10。的0.2％琼脂糖凝胶的混合物已经显示模拟体内由于CED引起凝胶扩张改变当地的孔隙分数。类似的毛孔小部分人脑类似的促进互动和VD 19的精确测量。此外，类似浓度的garose凝胶如0.6％和0.8％也显示类似输液压力分布至脑20。另外，透光性琼脂糖凝胶中提供的导管放置和输注回流的实时可视化的优点。琼脂糖凝胶假体是相对廉价的生产。琼脂糖凝胶假体的费用可能是关键，在整个神经外科未来的广泛培训。由于这些特性，琼脂糖凝胶提供了一个有用的替代，复制了许多人的大脑注入的关键属性，而无需使用脑组织。 如上所述，图像引导到CED琼脂糖凝胶模型提供的体外方法进行测试，研究和培训一个有益的。本文的目的是描述如何重新琼脂糖凝胶假体，勾勒适当CED测试和分析方案，并解决在CED输注用于神经系统疾病的治疗面临的常见错误。

<table border="0" cellpadding="0" cellspacing="0" width="590">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Prohance</td>
			<td style="width:71px;">Bracco</td>
			<td style="width:119px;"></td>
			<td style="width:195px;">Gadoteridol radio contrast media</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Bromophenol Blue Dye</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-0404</td>
			<td>Dye for infusate visualization</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:205px;">Agarose Gel Powder</td>
			<td style="width:71px;">Biorad</td>
			<td style="width:119px;">161-3101EDU</td>
			<td>Agarose powder for creating gels</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Veris MR Vital Signs Monitor</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pressure monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">16 Gauge SmartFlow Catheter</td>
			<td style="width:71px;">SurgiVision</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">Medrad Continuum MR Infusion System</td>
			<td style="width:71px;">Medrad</td>
			<td style="width:119px;"></td>
			<td>MR safe infusion pump</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:205px;">SMART Frame MRI Guided Trajectory Frame</td>
			<td style="width:71px;">ClearPoint</td>
			<td style="width:119px;"></td>
			<td>Infusion catheter frame</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:205px;">Osirix Imaging Software and DICOM Viewer</td>
			<td style="width:71px;">Osirix Imaging Software</td>
			<td style="width:119px;"></td>
			<td>OsiriX 32-bit DICOM Viewer</td>
		</tr>
	</tbody>
</table>

image-guided convection-enhanced delivery into agarose gel models of the brain

对流增强交付（CED）已被提议作为一个广泛的神经系统疾病的治疗选择。 Neuroinfusion导管海关允许正压大量流量，提供更大量疗法比传统给药方法颅内目标。实时磁共振成像的临床应用指导CED（rCED）在于准确瞄准，监测治疗，并确定并发症的能力。与训练，rCED是有效和并发症可以被最小化。大脑的琼脂糖凝胶模型提供了一种方便的工具CED测试，研究和培训。模拟大脑rCED允许模拟手术的做法，同时还提供可视化的输液反馈。输注的分析允许对分布分数（VD / VI）使学员以验证模型的相似性相比，人脑组织的计算。本文介绍了我们的琼脂糖凝胶假体脑并概述重要的我在同时解决过程中的CED输液面临神经系统疾病的治疗常见的陷阱，一个CED输液和分析协议trics。

解释和分析CED输液涉及的几个重要因素，如分配分数和输液回流。分配比例计算很大程度上取决于Vd的计算。因此，MR图像的准确解释是关键。我们提出了用于可靠地再现这些测量如上面列出的半自动化方法。这些方法客观地确定输液云和横截面面积的大致半径。而可变，在琼脂糖凝胶输液云往往被证明是球形的。假设一个球形输液云，该半径可以被用来确定在VD为CED输注。 VD / VI的琼脂糖凝胶输?...

Watch this Scientific Journal Video about Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain at JoVE.com

Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain

对流增强交付（CED）已被提议作为一个广泛的神经系统疾病的治疗选择。为了准备专业医护人员采用CED的，需要访问的培训模式。我们描述了使用琼脂糖凝胶作为人脑的这样的试验，研究和训练的模型。

图像引导的对流增强交付到大脑的琼脂糖凝胶模型

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows ...

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医学

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

异位黏膜移植程序直接给药到小鼠的大脑

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Mouse Kidney Transplantation: Models of Allograft Rejection

鼠肾移植：移植排斥反应模型

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

质粒DNA转座子介导整合到新生小鼠的脑室下区，以生成胶质母细胞瘤的新模型

An urgent need exists to test the contribution of new genes to the pathogenesis and progression of human glioblastomas (GBM), the most common primary ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

一种基于猪脑内皮细胞的体外血脑屏障模型的改进方法

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

持续药物输注系统对小鼠脑内下丘脑胰岛素信号的研究

Insulin regulates systematic metabolism in the hypothalamus and the peripheral insulin response. An inflammatory reaction in peripheral adipose tissues ...

Image-Guided Resection of Glioblastoma and Intracranial Implantation of Therapeutic Stem Cell-seeded Scaffolds

影像引导切除治疗干细胞种子支架的胶质母细胞瘤和颅内植入术

Glioblastoma (GBM), the most common and aggressive primary brain cancer, carries a life expectancy of 12-15 months. The short life expectancy is due in ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

用机器学习预测图像引导疗法的治疗反应--肝细胞癌的跨动脉治疗实例

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

大鼠中三极重化控制体积过载的图像引导透射斜线阀传单穿刺模型

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...

Intratracheal Administration of Dry Powder Formulation in Mice

小鼠干粉配方的内经管理

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...