Toward coupled multiphysics models of hemodynamics on leadership systems

领导系统血流动力学耦合多物理场模型

• 批准号: 8796995
• 负责人: Amanda E Randles
• 金额: $ 43.69万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2015-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8796995
• 关键词: 3D Print; Accounting; Address; Adhesions; Algorithms; Biological; Biological Process; Blood Circulation; Blood Pressure; Blood Vessels; Blood flow; Caliber; Cardiology; Cardiovascular system; Cause of Death; Cell Size; Cells; Cereals; Cessation of life; Clear Cell; Clinical Data; Collaborations; Complex; Computer Simulation; Coupled; Coupling; Data; Data Quality; Development; Diagnostic Neoplasm Staging; Disease; Disseminated Malignant Neoplasm; Frequencies; Geometry; Goals; Image; In Vitro; Leadership; Liquid substance; Location; Malignant Neoplasms; Measurement; Memory; Methods; Modeling; Movement; Neoplasm Circulating Cells; Neoplasm Metastasis; Normal Cell; Patients; Pattern; Penetration; Physiological; Process; Radiology Specialty; Relative (related person); Resolution; Risk; Sampling; Scheme; Site; System; Techniques; Testing; United States; Validation; Vascular System; Viscosity; Work; base; cancer cell; cancer site; cancer therapy; cell motility; circulating cancer cell; density; hemodynamics; improved; in vivo; insight; mathematical model; neglect; neoplastic cell; next generation; particle; public health relevance; research study; simulation; tumor

DESCRIPTION (provided by applicant): Cancer metastasis is responsible for more than 90% of cancer-related deaths and predicting the location of these secondary tumor sites remains an elusive goal. Studies have demonstrated that more than approximately two-thirds of cancer metastatic sites could be explained by the blood flow pattern between the primary and secondary sites. Development of a precise understanding of cell movement through the vascular system and the likelihood of penetration of the vessel wall is likely critical to achievin the ultimate goal of reliably predicting the vascular regions most likely to incur secondary tumor sites on a per-patient basis. A patient-specific method to predict these patterns will assist in cancer staging, enable identification of unknown primary sites, and inform next-generation treatment therapies that target cancer cells in circulation. We have developed a multiscale computational fluid dynamics model for assessing hemodynamics in image-based arterial geometries, and demonstrated its ability to accurately predict macroscopic quantities related to disease localization and progression. Based on this preliminary data, we hypothesize that (1) cell deformability impacts movement through the vasculature. (2) In vitro measurements can both quantify the range of cell-specific parameters and physiological states that should be used in assessing likely metastatic patterns and validate the computational models. (3) Case-specific simulations can predict likely secondary tumor sites. We propose three specific aims to test these hypotheses: Aim 1. Examine influence of cell deformability on the accurate models of CTC movement, and identify whether the method can be applied at the scale of the full-body. Aim 2. Validate large-scale computational models and predict in vitro measurements of values metastatic sites. Aim 3. Determine the ability of cell-specific computational models of the full-body to predict metastatic patterns observed in vivo. The goal of this application is to develop a method of predicting likely cancer metastasis sites through the use of massively parallel hemodynamic simulations at an unprecedented scale.

描述（由申请人提供）：90% 以上的癌症相关死亡是由癌症转移造成的，预测这些继发性肿瘤部位的位置仍然是一个难以实现的目标。研究表明，超过约三分之二的癌症转移部位可以通过原发部位和继发部位之间的血流模式来解释。准确理解细胞通过血管系统的运动和穿透血管壁的可能性对于实现可靠预测每个患者最有可能发生继发性肿瘤部位的血管区域的最终目标可能至关重要。预测这些模式的针对患者的特定方法将有助于癌症分期，能够识别未知的原发部位，并为针对循环中癌细胞的下一代治疗方法提供信息。我们开发了一种多尺度计算流体动力学模型，用于评估基于图像的动脉几何形状的血流动力学，并证明了其准确预测与疾病定位和进展相关的宏观量的能力。基于这些初步数据，我们假设 (1) 细胞变形性影响通过脉管系统的运动。 (2) 体外测量既可以量化细胞特异性参数和生理状态的范围，也可以用于评估可能的转移模式并验证计算模型。 (3)针对具体病例的模拟可以预测可能的继发性肿瘤部位。我们提出了三个具体目标来检验这些假设： 目标 1. 检查细胞变形性对 CTC 运动精确模型的影响，并确定该方法是否可以应用于全身尺度。目标 2. 验证大规模计算模型并预测转移部位的体外测量值。目标 3. 确定全身细胞特异性计算模型预测体内观察到的转移模式的能力。该应用程序的目标是开发一种通过以前所未有的规模使用大规模并行血流动力学模拟来预测可能的癌症转移部位的方法。