A computational model of glioma reveals opposing, stiffness-sensitive effects of leaky vasculature and tumor growth on tissue mechanical stress and porosity.
A computational model of glioma reveals opposing, stiffness-sensitive effects of leaky vasculature and tumor growth on tissue mechanical stress and porosity.
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DOI：
10.1007/s10237-021-01488-8
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发表时间：
2021-10
影响因子：
3.5
通讯作者：
Sarntinoranont, Malisa
中科院分区：
文献类型：
--
作者：
Rey, Julian A.;Ewing, James R.;Sarntinoranont, Malisa
开发了脑组织内生长的血管化胶质瘤的双相计算模型，以解释胶质瘤的独特特征，包括软的周围脑组织、其相对于脑组织的低硬度以及缺乏引流血管。该模型是第一个耦合非线性组织变形与孔隙率和组织导水率，研究机械相互作用的泄漏血管和固体生长在嵌入的胶质瘤。本模型显示，渗漏的脉管系统和升高的间质液压力在肿瘤内产生与肿瘤生长产生的压应力相反的张应力。这种拉伸效应在较软的组织中更明显，并导致肿瘤边缘处的压缩应力集中，当肿瘤比宿主软时，该压缩应力集中增加。除了产生固体应力之外，流体压力驱动的组织变形降低了肿瘤的有效刚度，而生长增加了肿瘤的有效刚度，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直接比较，证实了肿瘤边缘孔隙度降低的新预测。通过改变血管渗漏和组织导水率来模拟抗血管生成和放射治疗。这些分别导致肿瘤中更大的实体压缩和间质压力，前者可能促进肿瘤对宿主的浸润。我们的研究结果表明，血管渗漏有一个重要的影响，在体内的固体应力，刚度和孔隙率领域的胶质瘤，因为他们独特的机械微环境。
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 non-linear 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 produces 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.
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影响因子：
2.9
作者：
Ewing JR;Nagaraja TN;Aryal MP;Keenan KA;Elmghirbi R;Bagher-Ebadian H;Panda S;Lu M;Mikkelsen T;Cabral G;Brown SL
通讯作者：
Brown SL
影响因子：
3.3
作者：
Aryal, Madhava P.;Nagaraja, Tavarekere N.;Keenan, Kelly A.;Bagher-Ebadian, Hassan;Panda, Swayamprava;Brown, Stephen L.;Cabral, Glauber;Fenstermacher, Joseph D.;Ewing, James R.
通讯作者：
Ewing, James R.
放射治疗后小鼠脑肿瘤的纵向磁共振弹性成像研究
影响因子：
3.5
作者：
Feng Y;Clayton EH;Okamoto RJ;Engelbach J;Bayly PV;Garbow JR
通讯作者：
Garbow JR
影响因子：
6.6
作者：
BOWEN, RM
通讯作者：
BOWEN, RM
影响因子：
5.3
作者：
Fraldi, Massimiliano;Carotenuto, Angelo R.
通讯作者：
Carotenuto, Angelo R.