Convection-enhanced delivery is a technique to bypass the blood–brain barrier and deliver therapeutic drugs into the brain tissue. However, animal investigations and preliminary clinical trials have reported reduced efficacy to transport the infused drug in specific zones, attributed mainly to backflow, in which an annular gap is formed outside the catheter and the fluid preferentially flows toward the surface of the brain rather than through the tissue in front of the cannula tip. In this study, a three-dimensional human brain finite element model of backflow was developed to study the influence of anatomical structures during flow-controlled infusions. Predictions of backflow length were compared under the influence of ventricular pressure and the distance between the cannula and the ventricles. Simulations with zero relative ventricle pressure displayed similar backflow length predictions for larger cannula-ventricle distances. In addition, infusions near the ventricles revealed smaller backflow length and the liquid was observed to escape to the longitudinal fissure and ventricular cavities. Simulations with larger cannula-ventricle distances and nonzero relative ventricular pressure showed an increase of fluid flow through the tissue and away from the ventricles. These results reveal the importance of considering both the subject-specific anatomical details and the nonlinear effects in models focused on analyzing current and potential treatment options associated with convection-enhanced delivery optimization for future clinical trials.

对流增强递送是一种绕过血脑屏障并将治疗药物递送到脑组织中的技术。然而，动物研究和初步临床试验报告了在特定区域输送输注药物的效率降低，主要归因于回流，其中导管外形成环形间隙，液体优先流向大脑表面而不是通过套管尖端前面的组织。在这项研究中，开发了回流的三维人脑有限元模型，以研究在流量控制输注过程中解剖结构的影响。在心室压力和套管与心室之间的距离的影响下比较回流长度的预测。相对心室压力为零的模拟显示了对于较大套管-心室距离的类似回流长度预测。此外，靠近心室的输注显示较小的回流长度，观察到液体逃逸到纵向裂隙和心室腔。具有较大套管-心室距离和非零相对心室压力的模拟显示通过组织和远离心室的流体流量增加。这些结果揭示了在模型中考虑特定对象的解剖细节和非线性效应的重要性，这些模型专注于分析与未来临床试验的对流增强递送优化相关的当前和潜在治疗选择。靠近心室的输注显示回流长度较小，观察到液体逃逸到纵裂和心室腔。具有较大套管-心室距离和非零相对心室压力的模拟显示通过组织和远离心室的流体流量增加。这些结果揭示了在模型中考虑特定对象的解剖细节和非线性效应的重要性，这些模型专注于分析与未来临床试验的对流增强递送优化相关的当前和潜在治疗选择。靠近心室的输注显示回流长度较小，观察到液体逃逸到纵裂和心室腔。具有较大套管-心室距离和非零相对心室压力的模拟显示通过组织和远离心室的流体流量增加。这些结果揭示了在模型中考虑特定对象的解剖细节和非线性效应的重要性，这些模型专注于分析与未来临床试验的对流增强递送优化相关的当前和潜在治疗选择。具有较大套管-心室距离和非零相对心室压力的模拟显示通过组织和远离心室的流体流量增加。这些结果揭示了在模型中考虑特定对象的解剖细节和非线性效应的重要性，这些模型专注于分析与未来临床试验的对流增强递送优化相关的当前和潜在治疗选择。具有较大套管-心室距离和非零相对心室压力的模拟显示通过组织和远离心室的流体流量增加。这些结果揭示了在模型中考虑特定对象的解剖细节和非线性效应的重要性，这些模型专注于分析与未来临床试验的对流增强递送优化相关的当前和潜在治疗选择。