Abstract

Intra-arterial chemotherapy (IAC) is the preferred treatment for non-resectable hepatocellular carcinoma. A large fraction of IAC drugs, e.g., Doxorubicin, pass into systemic circulation, causing cardiac toxicity and reducing effectiveness of the procedure. These excessive drugs can be captured by the Chemofilter—a 3D-printable, catheter-based device deployed in a vein downstream of the liver during IAC. In this study, alternative configurations of the Chemofilter device were compared by evaluating their hemodynamic and filtration performance through multiphysics computational fluid dynamics simulations. Two designs were evaluated, a honeycomb-like structure of parallel hexagonal channels (honeycomb Chemofilter) and a cubic lattice of struts (strutted Chemofilter). The computationally optimized Chemofilter design contains three honeycomb stages, each perforated and twisted, which improved Doxorubicin adsorption by 44.6% compared to a straight channel design. The multiphysics simulations predicted an overall 66.8% decrease in concentration with a 2.9 mm-Hg pressure drop across the optimized device compared to a 50% concentration decrease observed during in-vivo experiments conducted with the strutted Chemofilter. The Doxorubicin transport simulations demonstrated the effectiveness of the Chemofilter in removing excessive drugs from circulation while minimizing pressure drop and eliminating flow stagnation regions prone to thrombosis. These results demonstrate the value of the multiphysics modeling approach in device optimization and experimental burden reduction.

中文翻译：

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化学过滤器中药物运输和混合的计算模型：增强循环中化学治疗剂的去除。

摘要

动脉内化疗（IAC）是不可切除肝细胞癌的首选治疗方法。大部分IAC药物（例如阿霉素）进入全身循环，引起心脏毒性并降低了该过程的有效性。这些过量的药物可以被化学过滤器捕获，这是一种3D可打印的，基于导管的设备，在IAC期间部署在肝脏下游的静脉中。在这项研究中，通过多物理场计算流体动力学模拟评估其血液动力学和过滤性能，比较了化学过滤器设备的替代配置。评估了两种设计，平行六边形通道的蜂窝状结构（蜂窝状化学过滤器）和支柱的立方晶格（被支撑的化学过滤器）。经过计算优化的化学过滤器设计包含三个蜂窝阶段，每个穿孔和扭曲，与直通道设计相比，阿霉素的吸附提高了44.6％。多物理场模拟预测，整个优化装置的浓度总体降低66.8％，而压降为2.9 mm-Hg，而在此期间观察到浓度降低了50％用支撑式化学过滤器进行的体内实验。阿霉素转运模拟证明了化学过滤器在从循环系统中去除过量药物的有效性，同时最大程度地降低了压降并消除了易于形成血栓的血流停滞区域。这些结果证明了多物理场建模方法在设备优化和减少实验负担方面的价值。