Orozco Gustavo A, Smith Joshua H, García José J
Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
Department of Mechanical Engineering, Lafayette College, Easton, PA, USA.
Proc Inst Mech Eng H. 2020 Sep;234(9):1018-1028. doi: 10.1177/0954411920937220. Epub 2020 Jul 9.
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至脑组织的技术。然而，动物研究和初步临床试验报告称，在特定区域输送注入药物的疗效降低，这主要归因于回流，即在导管外部形成一个环形间隙，流体优先流向脑表面而不是通过套管尖端前方的组织。在本研究中，建立了一个用于研究流动控制输注过程中解剖结构影响的三维人脑回流有限元模型。在心室压力和套管与心室之间距离的影响下，比较了回流长度的预测结果。在相对心室压力为零的模拟中，对于较大的套管 - 心室距离，显示出相似的回流长度预测。此外，在心室附近进行输注时，回流长度较小，并且观察到液体逸出到大脑纵裂和脑室腔中。在较大的套管 - 心室距离和非零相对心室压力的模拟中，显示通过组织并远离心室的流体流量增加。这些结果揭示了在专注于分析与对流增强递送优化相关的当前和潜在治疗方案以用于未来临床试验的模型中，考虑个体特异性解剖细节和非线性效应的重要性。
