E Quintero Jorge, Zhang Rui, Pang Qi, Xing Yi, Hardy Peter, Fan Xiaotong, Ai Yi, Gash Don M, A Gerhardt Greg, Grondin Richard, Zhang Zhiming
Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, United States; Department of Neurosurgery, College of Medicine, University of Kentucky, Lexington, KY, 40536, United States.
Department of Neurosurgery, Shandong Provincial Hospital, Shandong University School of Medicine, Jinan, Shandong, 250021, China.
J Neurosci Methods. 2021 Feb 1;349:109020. doi: 10.1016/j.jneumeth.2020.109020. Epub 2020 Dec 4.
Convection Enhanced Delivery (CED) into targeted brain areas has been tested in animal models and clinical trials for the treatment of various neurological diseases.
We used a series of techniques, to in effect, maintain positive pressure inside the catheter relative to the outside, that included a hollow stylet, a high volume bolus of solution to clear the line, a low and slow continuous flow rate during implantation, and heat sealing the catheter at the time of implantation.
120 catheters implanted into brain parenchyma of 89 adult female rhesus monkeys across four sets of experiments. After experiencing a high delivery failure rate - non patent catheters - (19 %) because of tissue entrapment and debris and/or blood clots in the catheter tip, we developed modifications, including increasing the bolus infusion volume from 10 to 20 μl such that by the third experiment, the failure rate was 8 % (1 of 12 implants). Increasing the bolus volume to 100 μl and maintaining positive pressure in the catheter during preparation and implantation yielded a failure rate of 0 % (0/12 implants) by the fourth experiment.
We provide a retrospective analysis to reveal how several different manipulations affect catheter patency and how post-op MRI examination is essential for assessing catheter patency in situ.
The results of the present study identified that the main cause of the catheter blockages were clots that rendered the catheter non-patent. We resolved this by modifying the surgical procedures that prevented these clots from forming.
对流增强递送(CED)进入目标脑区已在动物模型和临床试验中用于治疗各种神经系统疾病。
我们使用了一系列技术,以实际上保持导管内部相对于外部的正压,这些技术包括空心探针、大量溶液推注以清除管路、植入过程中低流速和缓慢的连续流速,以及在植入时对导管进行热封。
在四组实验中,将120根导管植入89只成年雌性恒河猴的脑实质中。由于组织嵌入以及导管尖端的碎片和/或血凝块,经历了较高的递送失败率——导管不通畅——(19%)之后,我们进行了改进,包括将推注输注体积从10 μl增加到20 μl,这样到第三次实验时,失败率为8%(12次植入中有1次)。在第四次实验时,将推注体积增加到100 μl并在准备和植入过程中保持导管内的正压,失败率为0%(0/12次植入)。
我们进行了一项回顾性分析,以揭示几种不同操作如何影响导管通畅性,以及术后MRI检查对于原位评估导管通畅性如何至关重要。
本研究结果表明,导管堵塞的主要原因是血凝块导致导管不通畅。我们通过修改手术程序解决了这个问题,该程序可防止这些血凝块形成。