IEEE Trans Biomed Eng. 2021 Apr;68(4):1229-1237. doi: 10.1109/TBME.2020.3024117. Epub 2021 Mar 18.
Hydraulic permeability is a topic of deep interest in biological materials because of its important role in a range of drug delivery-based therapies. The strong dependence of permeability on the geometry and topology of pore structure and the lack of detailed knowledge of these parameters in the case of brain tissue makes the study more challenging. Although theoretical models have been developed for hydraulic permeability, there is limited consensus on the validity of existing experimental evidence to complement these models. In the present study, we measure the permeability of white matter (WM) of fresh ovine brain tissue considering the localised heterogeneities in the medium using an infusion-based experimental set up, iPerfusion. We measure the flow across different parts of the WM in response to applied pressures for a sample of specific dimensions and calculate the permeability from directly measured parameters. Furthermore, we directly probe the effect of anisotropy of the tissue on permeability by considering the directionality of tissue on the obtained values. Additionally, we investigate whether WM hydraulic permeability changes with post-mortem time. To our knowledge, this is the first report of experimental measurements of the localised WM permeability, also demonstrating the effect of axon directionality on permeability. This work provides a significant contribution to the successful development of intra-tumoural infusion-based technologies, such as convection-enhanced delivery (CED), which are based on the delivery of drugs directly by injection under positive pressure into the brain.
液压渗透性是生物材料中一个非常感兴趣的话题，因为它在多种基于药物输送的治疗中起着重要作用。渗透性强烈依赖于孔结构的几何形状和拓扑结构，而脑组织中这些参数的详细知识却缺乏，这使得研究更加具有挑战性。尽管已经为液压渗透性开发了理论模型，但对于现有实验证据的有效性存在有限的共识，这些证据可以补充这些模型。在本研究中，我们使用基于灌注的实验设置 iPerfusion，考虑到介质中的局部不均匀性，测量了新鲜绵羊脑组织白质 (WM) 的渗透性。我们测量了在特定尺寸的样本中，响应施加的压力，在 WM 的不同部位的流量，并直接从直接测量的参数计算渗透性。此外，我们通过考虑组织的各向异性对渗透性的影响，直接探测组织各向异性对渗透性的影响。此外，我们还研究了 WM 液压渗透性是否随死后时间而变化。据我们所知，这是首次对局部 WM 渗透性进行实验测量的报告，也证明了轴突方向性对渗透性的影响。这项工作为成功开发基于肿瘤内灌注的技术（如对流增强输送 (CED)）做出了重要贡献，这些技术基于在大脑中直接通过正压注射将药物输送到肿瘤内。
