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脑胶质瘤的计算模型揭示了渗漏血管和肿瘤生长对组织力学应力和孔隙率的相反的、对刚性敏感的影响。

A computational model of glioma reveals opposing, stiffness-sensitive effects of leaky vasculature and tumor growth on tissue mechanical stress and porosity.

机构信息

Department of Mechanical and Aerospace Engineering, University of Florida, PO BOX 116250, Gainesville, FL, 32611, USA.

Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.

出版信息

Biomech Model Mechanobiol. 2021 Oct;20(5):1981-2000. doi: 10.1007/s10237-021-01488-8. Epub 2021 Aug 7.

Abstract

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.

摘要

开发了一个两相计算模型,用于模拟脑内生长的血管化神经胶质瘤,以解释神经胶质瘤的独特特征,包括周围柔软的脑组织、相对于脑组织的低硬度以及缺乏引流的淋巴管。该模型是第一个将非线性组织变形与孔隙率和组织水力传导率相结合,以研究渗漏血管和嵌入神经胶质瘤中实体生长的力学相互作用的模型。目前的模型表明,渗漏血管和升高的间质流体压力会在肿瘤内产生与肿瘤生长产生的压缩应力相反的张应力。这种拉伸效应在较软的组织中更为明显,导致肿瘤边缘的压缩应力集中增加,而肿瘤比宿主更软时则会增加。除了产生固体应力外,流体压力驱动的组织变形会降低肿瘤的有效刚度,而生长会增加其刚度,这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的估计值进行直接比较,证实了肿瘤边缘孔隙率降低的新预测。通过改变血管通透性和组织水力传导率来模拟抗血管生成和放射治疗。这分别导致肿瘤内的固体压缩和间质压力增加,前者可能促进肿瘤向宿主浸润。我们的研究结果表明,鉴于神经胶质瘤独特的力学微环境,血管通透性对神经胶质瘤的体内固体应力、刚度和孔隙率场有重要影响。

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