Computational and theoretical fluid mechanics modeling for transport in dense tumors

致密肿瘤中运输的计算和理论流体力学模型

• 批准号: 10817669
• 负责人: Saikat Basu
• 金额: $ 13.48万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10817669
• 关键词: Benchmarking; Blood Vessels; Cancerous; Cell Culture Techniques; Clinical; Convection; Data; Diagnostic; Diffusion; Endothelium; Environment; Extracellular Matrix; Extracellular Space; Fiber; Geometry; Human; Implant; Liquid substance; Literature; Malignant neoplasm of pancreas; Mechanics; Medical; Microfluidics; Modeling; Mus; Necrosis; Perfusion; Phase; Plasma; Resort; Scanning; Shapes; Slice; Solid; Solid Neoplasm; Starling (law); Stress; Structure; System; Testing; Theoretical model; Therapeutic; Vision; Work; X-Ray Computed Tomography; cancer care; cancer diagnosis; clinical diagnosis; design; experimental study; image processing; in silico; logarithm; novel diagnostics; pancreatic neoplasm; simulation; tool; trend; tumor; tumor microenvironment; uptake; usability

Intratumoral perfusion has long been recognized as a critical issue in both clinical diagnosis and therapy of dense solid cancerous tumors. In such context, a first-principles mechanics-based model that can quantify perfusion in the intratumoral extracellular spaces as a function of the tumor vasculature shapes and the fiber packing fraction in the stroma – can launch new avenues in cancer diagnosis and care. With that vision, the proposed project will integrate computational fluid dynamics (CFD) tracking with theoretical fluid mechanics analysis to generate an in silico tumor uptake modeling framework, that can operate over a wide parametric space. The test geometries will be based off computed tomography (CT) scans of human pancreatic tumors implanted in mice. The project will also design supplementary physical experiments in microfluidic setups and artificial tumor spheroids to benchmark and validate the proposed in silico approach. With use of mean continuum-level transport frameworks such as Darcy's Law and Starling model still a go-to resort for basic fluids modeling of intratumoral uptake quantification, the proposed CFD-informed advanced theoretical fluid mechanics approach to parameterize tumor perfusion based on tumor geometry and intratumoral stress will constitute this project's key contribution to the literature. The long-term objective of the project is as follows: in a clinical setting, the packing fraction of the fiber bundles inside the stroma can be readily assessed from image-processing the CT-slices from a tumor, it being logarithmically proportional to the intratumoral stress. The proposed numerical-theoretical model will be designed such as to project the tumoral uptake as a function of the packing fraction. This can trigger new diagnostic/therapeutic solutions with the fluidic transport trends inside a solid tumor predictable solely from the medical scans through assessment of the packing fraction. Our central hypothesis is: an integration of numerical computations with theoretical modeling can cover a diverse range of tumor microenvironments, rendering greater usability for the fluid mechanics tools. The resulting in silico framework will generate percolation data over a wide parameter space of tumor geometry features, e.g., the packing fraction inside the stroma and the local curvatures of blood vessels in the tumor vasculature. The work is structured around the following specific aims: (a) Aim 1 will numerically simulate multiphase transport inside the tumor vasculature, considering realistic blood vessel shapes and electrohydrodynamic effects on the mean transport, (b) Aim 2 will import from Aim 1 the plasma dynamics information at the endothelial openings and use the data as initial conditions to develop an integrative numerical-theoretical model for intratumoral transport through the extracellular matrix. The theoretical setup will invoke a convection-diffusion approach, where the boundary conditions on the local concentrations at the tumor inlet and near the necrotic core (deep into the tumor) will be fed from the numerical simulations. Finally, the in silico perfusion predictions will be compared against physical experiments performed in simplified bio-inspired microfluidic systems and with cell culture-derived realistic tumor spheroids embedded in a fluidic environment.

长期以来，肿瘤内灌注已被认为是临床诊断和致密固体癌性肿瘤治疗的关键问题。在这种情况下，基于第一原理的机制模型可以量化肿瘤内细胞外空间中的灌注，这是肿瘤脉管形状的函数和基质中的纤维堆积分数 - 可以在癌症诊断和护理中引发新的途径。有了该视觉，提出的项目将将计算流体动力学（CFD）跟踪与理论流体力学分析集成，以生成一个可以在广泛的参数空间中运行的硅肿瘤吸收建模框架。测试几何技术将基于植入小鼠的人胰腺肿瘤的计算机断层扫描（CT）扫描。该项目还将在微流体设置和人造肿瘤球体中设计补充物理实验，以基准测试并验证硅方法中提出的。通过使用平均连续水平的运输框架，例如达西定律和Starling模型，仍然是对肿瘤内吸收量化量化的基本流体建模的首选措施，拟议中的CFD提出的先进的高级理论机制方法可以将肿瘤灌注的参数化基于肿瘤的几何形状和肿瘤灌注，并构成该项目的关键贡献。该项目的长期目的如下：在临床环境中，可以通过图像处理从肿瘤中的CT处理来评估基质内部的纤维束的包装部分，在对数与肿瘤内应力的对数上是对数。提出的数字理论模型将设计，例如将肿瘤摄取作为包装部分的函数。这可以触发新的诊断/治疗溶液，而实体瘤内部的流体运输趋势仅通过评估包装部分就可以通过医疗扫描来预测。我们的中心假设是：将数值计算与理论建模的集成可以涵盖潜水员的肿瘤微环境，从而使流体机械工具的可用性更大。在肿瘤几何特征的广泛参数空间上，例如，基质框架的渗透率数据，例如，基质内部的堆积分数以及肿瘤血管中血管的局部曲率。这项工作是围绕以下特定目的进行结构的：（a）目标1将单独模拟肿瘤脉管系统内的多相传输，考虑到逼真的血管形状和对平均运输的电氢动力学效应，（b）目标2将从目标1中进口，目的1将从目标中进口，以在底层开放中开发数据，并将其用于整体的数值，以实现数据的临时运输，以实现整体的模型，以实现整体模型，以实现整体的模型 矩阵。理论设置将调用对话扩散方法，其中肿瘤入口和坏死核附近的局部浓度（深入肿瘤）的边界条件将从数字模拟中馈送。最后，将在简化的生物启发的微流体系统以及嵌入流体环境中嵌入的细胞培养的逼真的逼真的肿瘤球体中进行比较，与在简化的生物启发的微流体系统中进行的物理实验进行比较。