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: 8931819
• 负责人: Amanda E Randles
• 金额: $ 39.17万
• 依托单位: DUKE UNIVERSITY
• 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 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8931819
• 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; Health; 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; research study; simulation; targeted treatment; 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）：癌症转移负责超过90％的与癌症相关的死亡，并预测这些继发性肿瘤部位的位置仍然是一个难以捉摸的目标。研究表明，大约三分之二的癌症转移性部位可以通过初级和次要部位之间的血流模式来解释。开发通过血管系统对细胞运动的精确理解以及血管壁渗透的可能性对于Achievin来说可能是至关重要的，这是可靠地预测最有可能在每个患者中引起次生肿瘤部位的血管区域的最终目标。一种预测这些模式的患者特异性方法将有助于癌症分期，能够鉴定未知的原始部位，并告知针对循环癌细胞的下一代治疗疗法。我们已经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中的血液动力学，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。基于此初步数据，我们假设（1）细胞变形性会影响通过脉管系统的运动。 （2）体外测量值既可以量化细胞特异性参数和生理状态的范围，这些参数应用于评估可能的转移模式并验证计算模型。 （3）特异性模拟可以预测可能的次要肿瘤部位。我们提出了三个特定的目的，以检验这些假设：目标1。检查细胞变形性对CTC运动准确模型的影响，并确定该方法是否可以在全身的尺度上应用。 AIM 2。验证大规模计算模型并预测值转移位点的体外测量。目标3。确定全身的细胞特异性计算模型预测体内观察到的转移模式。该应用的目的是通过在前所未有的规模上使用大量平行的血流动力学模拟来开发一种预测可能的癌症转移部位的方法。