根据 DCE-MRI 对大鼠 U251N 正位胶质瘤的异质机械应力和间质流体流动进行预测

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL
Julian A. Rey, Katelynn G. Spanick, Glauber Cabral, Isabel N. Rivera-Santiago, Tavarekere N. Nagaraja, Stephen L. Brown, James R. Ewing, Malisa Sarntinoranont
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引用次数: 0

摘要

体外的机械应力和流体流动会影响胶质瘤细胞的表型,但在体内测量这些量仍然具有挑战性。本研究的目的是预测体内的这些量,从而深入了解胶质瘤的生理学和潜在的机械生物标志物,从而改善胶质瘤的检测、诊断和治疗。研究人员开发了基于图像的无胸腺大鼠人类 U251N 正位胶质瘤有限元模型,以预测每只动物肿瘤内部和周围的结构应力和间质流动。除了考虑肿瘤生长引起的结构应力外,我们的方法还具有捕捉流体压力引起的结构应力的优势,而这是通过体内间质流体压力(IFP)测量获得的。由于胶质瘤和大脑都很柔软,IFP 的升高大大增加了肿瘤的结构应力,甚至在顺应性最强的病例中,这种应力从压缩应力反转为拉伸应力。肿瘤生长和 IFP 升高的共同作用导致结构应力集中在肿瘤边界附近,而肿瘤边界是最有可能影响细胞增殖和侵袭的地方。核磁共振成像衍生的解剖几何结构和组织特性分布导致间质流体异质性流动,在脑脊液空间附近出现局部最大值,这可能会促进肿瘤侵袭并阻碍药物输送。此外,预测的结构应力和间质流在受辐射动物和未受辐射动物之间存在明显差异。我们的建模表明,相对于较硬组织中的肿瘤,神经胶质瘤经历了不寻常的机械条件,可能会产生重要的生物学后果(如增殖和侵袭)和临床后果(如给药和治疗监测)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Heterogeneous Mechanical Stress and Interstitial Fluid Flow Predictions Derived from DCE-MRI for Rat U251N Orthotopic Gliomas

Heterogeneous Mechanical Stress and Interstitial Fluid Flow Predictions Derived from DCE-MRI for Rat U251N Orthotopic Gliomas

Mechanical stress and fluid flow influence glioma cell phenotype in vitro, but measuring these quantities in vivo continues to be challenging. The purpose of this study was to predict these quantities in vivo, thus providing insight into glioma physiology and potential mechanical biomarkers that may improve glioma detection, diagnosis, and treatment. Image-based finite element models of human U251N orthotopic glioma in athymic rats were developed to predict structural stress and interstitial flow in and around each animal's tumor. In addition to accounting for structural stress caused by tumor growth, our approach has the advantage of capturing fluid pressure-induced structural stress, which was informed by in vivo interstitial fluid pressure (IFP) measurements. Because gliomas and the brain are soft, elevated IFP contributed substantially to tumor structural stress, even inverting this stress from compressive to tensile in the most compliant cases. The combination of tumor growth and elevated IFP resulted in a concentration of structural stress near the tumor boundary where it has the greatest potential to influence cell proliferation and invasion. MRI-derived anatomical geometries and tissue property distributions resulted in heterogeneous interstitial fluid flow with local maxima near cerebrospinal fluid spaces, which may promote tumor invasion and hinder drug delivery. In addition, predicted structural stress and interstitial flow varied markedly between irradiated and radiation-naïve animals. Our modeling suggests that relative to tumors in stiffer tissues, gliomas experience unusual mechanical conditions with potentially important biological (e.g., proliferation and invasion) and clinical consequences (e.g., drug delivery and treatment monitoring).

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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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