Abstract

Background: Thermoembolization presents a unique treatment alternative for patients diagnosed with hepatocellular carcinoma. The approach delivers a reagent that undergoes an exothermic chemical reaction and combines the benefits of embolic as well as thermal- and chemical-ablative therapy modalities. The target tissue and vascular bed are subjected to simultaneous hyperthermia, ischemia, and chemical denaturation in a single procedure. To guide optimal delivery, we developed a mathematical model for understanding the competing diffusive and convective effects observed in thermoembolization delivery protocols.

Methods: A mixture theory formulation was used to mathematically model thermoembolization as chemically reacting transport of an electrophile, dichloroacetyl chloride (DCACl), within porous living tissue. Mass and energy transport of each relevant constituent are considered. Specifically, DCACl is injected into the vessels and exothermically reacts with water in the blood or tissue to form dichloroacetic acid and hydrochloric acid. Neutralization reactions are assumed instantaneous in this approach. We validated the mathematical model predictions of temperature using MR thermometry of the thermoembolization procedure performed in ex vivo kidney.

Results: Mathematical modeling predictions of tissue death were highly dependent on the vascular geometry, injection pressure, and intrinsic amount of exothermic energy released from the chemical species, and were able to recapitulate the temperature distributions observed in MR thermometry.

Conclusion: These efforts present a first step toward formalizing a mathematical model for thermoembolization and are promising for providing insight for delivery protocol optimization. While our approach captured the observed experimental temperature measurements, larger-scale experimental validation is needed to prioritize additional model complexity and fidelity.

摘要

背景：热栓塞为诊断为肝细胞癌的患者提供了一种独特的治疗选择。该方法提供了一种经历放热化学反应的试剂，并结合了栓塞以及热和化学消融治疗方式的优点。在一次手术中，靶组织和血管床同时受到高温、缺血和化学变性。为了指导最佳输送，我们开发了一个数学模型来理解热栓塞输送方案中观察到的竞争扩散和对流效应。

方法：使用混合理论公式对热栓塞进行数学建模，即亲电子试剂二氯乙酰氯 (DCACl) 在多孔活组织内发生化学反应运输。考虑每个相关成分的质量和能量传输。具体而言，DCACl被注入血管并与血液或组织中的水发生放热反应，形成二氯乙酸和盐酸。在该方法中，假定中和反应是瞬时发生的。我们使用在离体肾脏中进行的热栓塞程序的 MR 测温法验证了温度的数学模型预测。

结果：组织死亡的数学模型预测高度依赖于血管几何形状、注射压力和化学物质释放的固有放热能量，并且能够概括在 MR 测温中观察到的温度分布。

结论：这些努力为热栓塞数学模型的形式化迈出了第一步，并有望为输送方案优化提供见解。虽然我们的方法捕获了观察到的实验温度测量结果，但需要更大规模的实验验证来优先考虑额外的模型复杂性和保真度。