Elenes Egleide Y, Rausch Manuel K, Rylander Christopher G
Department of Biomedical Engineering, University of Texas at Austin, 107 W. Dean Keeton Street, Stop C0800, Austin, TX 78712 e-mail:
Department of Aerospace Engineering and Engineering Mechanics, University of Texas at Austin, 2617 Wichita Street, Stop C0600, Austin, TX 78712-1221; Department of Biomedical Engineering, University of Texas at Austin, 107 W. Dean Keeton Street, Stop C0800, Austin, TX 78712 e-mail:
J Eng Sci Med Diagn Ther. 2019 Aug;2(3):0310021-310029. doi: 10.1115/1.4042874. Epub 2019 Apr 1.
Convection-enhanced delivery (CED) is an investigational therapy developed to circumvent the limitations of drug delivery to the brain. Catheters are used in CED to locally infuse therapeutic agents into brain tissue. CED has demonstrated clinical utility for treatment of malignant brain tumors; however, CED has been limited by lack of CED-specific catheters. Therefore, we developed a multiport, arborizing catheter to maximize drug distribution for CED. Using a multiphasic finite element (FE) framework, we parametrically determined the influence of design variables of the catheter on the dispersal volume of the infusion. We predicted dispersal volume of a solute infused in a permeable hyperelastic solid matrix, as a function of separation distance (ranging from 0.5 to 2.0 cm) of imbedded infusion cavities that represented individual ports in a multiport catheter. To validate the model, we compared FE solutions of pressure-controlled infusions to experimental data of indigo carmine dye infused in agarose tissue phantoms. The T, defined as the infusion time required for the normalized solute concentration between two sources to equal 50% of the prescribed concentration, was determined for simulations with infusion pressures ranging from 1 to 4 kPa. In our validated model, we demonstrate that multiple ports increase dispersal volume with increasing port distance but are associated with a significant increase in infusion time. T increases approximately tenfold when doubling the port distance. Increasing the infusion flow rate (from 0.7 L/min to 8.48 L/min) can mitigate the increased infusion time. In conclusion, a compromise of port distance and flow rate could improve infusion duration and dispersal volume.
对流增强递送（CED）是一种为克服药物向脑内递送的局限性而开发的研究性治疗方法。在CED中使用导管将治疗剂局部注入脑组织。CED已证明对治疗恶性脑肿瘤具有临床实用性；然而，CED一直受到缺乏CED专用导管的限制。因此，我们开发了一种多端口分支导管，以最大限度地提高CED的药物分布。使用多相有限元（FE）框架，我们参数化地确定了导管设计变量对输注分散体积的影响。我们预测了注入可渗透超弹性固体基质中的溶质的分散体积，作为代表多端口导管中各个端口的嵌入式输注腔分离距离（范围为0.5至2.0厘米）的函数。为了验证该模型，我们将压力控制输注的有限元解与注入琼脂糖组织模型中的靛蓝胭脂红染料的实验数据进行了比较。对于输注压力范围为1至4kPa的模拟，确定了T，T定义为两个源之间归一化溶质浓度等于规定浓度的50%所需的输注时间。在我们经过验证的模型中，我们证明多个端口随着端口距离的增加而增加分散体积，但与输注时间的显著增加相关。当端口距离加倍时，T增加约十倍。增加输注流速（从0.7L/min增加到8.48L/min）可以减轻输注时间的增加。总之，端口距离和流速的折衷可以改善输注持续时间和分散体积。
