Background

Convection Enhanced Delivery (CED) into targeted brain areas has been tested in animal models and clinical trials for the treatment of various neurological diseases.

New method

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.

Results

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.

Comparison with existing methods

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.

Conclusions

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.

中文翻译：

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防止在神经外科手术期间和之后阻塞植入的脑导管的手术方法和协议

背景

对流增强递送（CED）进入目标脑区域已在动物模型和临床试验中进行了测试，用于治疗各种神经系统疾病。

新方法

我们使用了一系列技术来有效地保持导管内部相对于外部的正压力，包括空心探针，高剂量的溶液清除团块，植入过程中缓慢且缓慢的连续流速，以及植入时热封导管。

结果

在四组实验中，将120根导管植入到89只成年雌性猕猴的脑实质中。由于组织尖端和导管尖端的碎屑和/或血凝块而导致较高的输送失败率–非专利导管–（19％），我们进行了改进，包括将推注输注量从10μl增加到20μl在第三个实验中，失败率为8％（12个植入物中的1个）。在第四个实验中，将推注体积增加至100μl，并在准备和植入过程中保持导管中的正压可导致失败率为0％（0/12个植入物）。

与现有方法的比较

我们提供了一项回顾性分析，以揭示几种不同的操作如何影响导管通畅，以及术后MRI检查对于评估原位导管通畅如何必不可少。

结论

本研究的结果确定，导管阻塞的主要原因是凝块，导致导管非专利。我们通过修改防止这些凝块形成的外科手术程序解决了这一问题。