A biphasic computational model of a growing, vascularized glioma within brain tissue was developed to account for unique features of gliomas, including soft surrounding brain tissue, their low stiffness relative to brain tissue, and a lack of draining lymphatics. This model is the first to couple nonlinear tissue deformation with porosity and tissue hydraulic conductivity to study the mechanical interaction of leaky vasculature and solid growth in an embedded glioma. The present model showed that leaky vasculature and elevated interstitial fluid pressure produce tensile stress within the tumor in opposition to the compressive stress produced by tumor growth. This tensile effect was more pronounced in softer tissue and resulted in a compressive stress concentration at the tumor rim that increased when tumor was softer than host. Aside from generating solid stress, fluid pressure-driven tissue deformation decreased the effective stiffness of the tumor while growth increased it, potentially leading to elevated stiffness in the tumor rim. A novel prediction of reduced porosity at the tumor rim was corroborated by direct comparison with estimates from our in vivo imaging studies. Antiangiogenic and radiation therapy were simulated by varying vascular leakiness and tissue hydraulic conductivity. These led to greater solid compression and interstitial pressure in the tumor, respectively, the former of which may promote tumor infiltration of the host. Our findings suggest that vascular leakiness has an important influence on in vivo solid stress, stiffness, and porosity fields in gliomas given their unique mechanical microenvironment.

开发了脑组织内生长的、血管化的神经胶质瘤的双相计算模型，以解释神经胶质瘤的独特特征，包括周围脑组织柔软、相对于脑组织的低硬度以及缺乏引流淋巴管。该模型是第一个将非线性组织变形与孔隙率和组织导水率相结合，以研究嵌入式神经胶质瘤中渗漏血管和实体生长的机械相互作用。本模型显示，与肿瘤生长产生的压应力相反，渗漏的脉管系统和升高的间质液压力在肿瘤内产生张应力。这种拉伸效应在较软的组织中更为明显，并导致肿瘤边缘处的压缩应力集中，当肿瘤比宿主更柔软时，压缩应力会增加。除了产生固体应力外，流体压力驱动的组织变形降低了肿瘤的有效刚度，而生长增加了它，可能导致肿瘤边缘的刚度升高。通过与我们的体内成像研究估计值的直接比较，证实了肿瘤边缘孔隙率降低的新预测。抗血管生成和放射治疗通过不同的血管渗漏和组织水力传导率来模拟。这些分别导致肿瘤中更大的实体压缩和间质压力，前者可能促进宿主的肿瘤浸润。我们的研究结果表明，鉴于其独特的机械微环境，血管渗漏对胶质瘤的体内固体应力、刚度和孔隙率场具有重要影响。流体压力驱动的组织变形降低了肿瘤的有效刚度，而生长增加了它，可能导致肿瘤边缘的刚度升高。通过与我们的体内成像研究估计值的直接比较，证实了肿瘤边缘孔隙率降低的新预测。抗血管生成和放射治疗通过不同的血管渗漏和组织水力传导率来模拟。这些分别导致肿瘤中更大的实体压缩和间质压力，前者可能促进宿主的肿瘤浸润。我们的研究结果表明，鉴于其独特的机械微环境，血管渗漏对胶质瘤的体内固体应力、刚度和孔隙率场具有重要影响。流体压力驱动的组织变形降低了肿瘤的有效刚度，而生长增加了它，可能导致肿瘤边缘的刚度升高。通过与我们的体内成像研究估计值的直接比较，证实了肿瘤边缘孔隙率降低的新预测。抗血管生成和放射治疗通过不同的血管渗漏和组织水力传导率来模拟。这些分别导致肿瘤中更大的实体压缩和间质压力，前者可能促进宿主的肿瘤浸润。我们的研究结果表明，鉴于其独特的机械微环境，血管渗漏对胶质瘤的体内固体应力、刚度和孔隙率场具有重要影响。