COMPUTATIONAL FLUID DYNAMICS FOR THE HEMODYNAMIC INVESTIGATION OF PEDIATRIC CAR

用于儿科车血流动力学研究的计算流体动力学

• 批准号: 7723323
• 负责人: Kerem Pekkan
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723323
• 关键词: Abdomen; Abdominal Aortic Aneurysm; Address; Affect; Age; Anatomy; Aneurysm; Angiography; Angioplasty; Animal Model; Aorta; Aortic Arch Syndromes; Arts; Beds; Biomechanics; Biomedical Engineering; Bite; Blood; Blood Circulation; Blood Flow Velocity; Blood Pressure; Blood flow; Brain Injuries; Bypass; Cannulas; Cannulations; Cardiac; Cardiac Output; Cardiac Surgery procedures; Cardiopulmonary; Cardiopulmonary Bypass; Cardiovascular system; Catheters; Cephalic; Cerebrovascular Circulation; Cerebrum; Characteristics; Chick Embryo; Chickens; Child; Childhood; Circle of Willis; Classification; Clinic; Clinical; Complex; Computer Assisted; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computer software; Computer-Aided Design; Condition; Congenital Heart Defects; Coronary Artery Bypass; Coronary artery; Coupled; Data; Data Storage and Retrieval; Decision Making; Depth; Descending aorta; Development; Disease; Dorsal; Drops; Echocardiography; Elements; Embryo; Endothelin-1; Engineering; European; Exercise Tolerance; Failure; Funding; Future; Gene Proteins; Generations; Generic Drugs; Grant; Head and neck structure; Health; Hemolysis; High Cardiac Output; High Performance Computing; Hour; Human; Imagery; In Vitro; Individual; Inflammation; Institution; Investigation; Journals; Labyrinth fenestration; Left; Left pulmonary artery; Life; Ligation; Linux; Liquid substance; Literature; Magnetic Resonance Imaging; Measures; Methodology; Modeling; Neonatal; Numbers; Operative Surgical Procedures; Organ; Outcome; Patients; Pattern; Perfusion; Physiological; Physiology; Pregnancy; Process; Property; Pulsatile Flow; Purpose; Quality of life; Reconstructive Surgical Procedures; Research; Research Personnel; Resources; Risk; Role; Running; Scanning; Shapes; Side; Simulate; Solutions; Source; Speed; Staging; Standards of Weights and Measures; Steno; Stenosis; Stress; Structure; Superior vena cava structure; Surgeon; System; Techniques; Technology; Thick; Time; TimeLine; Translating; Tube; Ultrasonography; United States National Institutes of Health; Universities; Variant; Venous; Walkers; Work; Yolk Sac; aortic arch; ascending aorta; base; biomechanical engineering; computer studies; congenital heart disorder; design; egg; embryo circulation; experience; fluorescence microscope; hemodynamics; improved; in utero; in vivo; indexing; interest; neonate; pressure; protein expression; reconstruction; research study; shear stress; simulation; symposium; three-dimensional modeling; tool; virtual; viscoelasticity

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Purpose: The objectives of our computational fluid dynamics (CFD) studies are i) to optimize the orientation and design of the pediatric canullation techniques during neonatal/pediatric cardiopulmonary bypass (CPB), particularly we like to extent our current work [1] to complex reconstructive surgeries of the hypoplastic aortic arch syndrome ii) to investigate the role of flow-driven hemodynamic loading on the development of the aortic arches (abnormal loading conditions can cause complex heart defects) [2,4] (iii) to advance and enable cyber-enabled pre-surgical cardiovascular planning in complex reconstructive surgeries. Introduction and Research Aims: Coupled with the accurate reconstructions of anatomical data (via MRI, angiograms, echocardiograms and CT) CFD simulation technologies have been increasingly recognized as a surgical planning tool for the cardiovascular systems. Example studies include abdominal aortic aneurism [5-6], arterial stenosis [7], coronary arteries [8] and congenital heart diseases (CHD) [9,10]. The research interest in such patient-specific modeling CFD applications currently move from analysis towards systematic geometric optimization and require high performance computing power. To illustrate the scope of the problem, typical numbers from a standard transient anatomic 3D CFD result (n=1) which require ~125Gb of storage space for the raw data (and ~1week of CPU time in a single-PI 16 node cluster) can be considered. For each anatomy reconstruction 15 of these solutions are needed, typically for three cardiac outputs. The raw data of this CFD modeling effort alone require ~2.4Terabytes of temporary and permanent data storage systems. Referring to our first research aim, pediatric canullation constitutes a key element for the staged palliation of complex congenital heart defects which requires open heart surgeries very early in life. Prolonged cardiopulmonary bypass (CPB) usually required during these surgeries affecting 20,000 children annually. Standard CPB techniques on neonates [11] are known to be very detrimental, including higher inflammation risk, premature Circle of Willis [12], unbalanced, non-physiological organ perfusion [13, 14] resulting in temporary or permanent brain damage up to 25% of patients. Therefore, there is an urgent need to optimize the biomechanical design of pediatric/neonatal CPB circuit components, which is challenged by complex pulsatile and cavitating flows, has to be customized for the patient-specific anatomy and physiology. Our second research aim investigating the flow-driven hemodynamic loading addresses the form-flow relationship on the development of aortic arches. Although the altered (abnormal) venous flow patterns have been confirmed as the major reasons for the CHD by systematic in vivo flow visualization studies [15], engineering fluid dynamic analysis tools are recently advanced to support the quantification of these observations. Essentially, quantification of these flow alterations during the cardiac development is critical for defining the mechanism responsible for clinically prevalent heart defects (1 in 100 children) and in optimizing their in-utero and post-natal management. Recently our group has also embarked upon attempting to cyber-enabled pre-surgical cardiovascular planning by virtually modifying and optimizing anatomical MRI reconstructions at the clinic or at the bed-side using computer aided tools and simulating flow using CFD. The proposed methodology is illustrated in Figure 1. Cutting-edge high performance computing is again essential for all steps of this process namely, pre-processing, solver and post-processing. Since the pre-surgical clinical decision will be based on at least ~10 different candidate parametric anatomies for each patient the total row data of this CFD modeling effort will alone require ~24Terabytes of storage. Although the amount of CFD data generated for a single patient is quite large and at present practically inaccessible on a routine basis, there is a clear benefit for the patients health to undertake this effort. Clinically this corresponds to improved quality of life with higher cardiac outputs and better exercise tolerance. Example Methodology: Pediatric CPB: A virtual CPB is created on the 3D cardiac MRI reconstruction of a pediatric patient (Age: 12.5, BSA: 1.32m2) with a normal aortic arch by clamping the ascending aorta and inserting the computer-aided design model of the 10Fr tapered generic cannula. Cannula and aortic arch are oriented with respect to each other to simulate a typical standard pediatric CPB configuration. Pulsatile 3D blood flow velocities and pressures are computed using the commercial computational fluid dynamics (CFD) software (Fluent, ANSYS Inc.) using the 2nd order accurate experimentally validated solver [3]. Simulations are performed on a parallel Linux cluster by invoking twenty nodes each with 3.2 GHz 32 bit Intel Pentium4 processors simultaneously. Computations took approximately 72 hours to simulate three converged cycles with a period of 0.635 seconds. Cannula inlet flow waveform is measured from in vivo PC-MRI and piglet animal model physiological experiments (with DLP75010 cannula), distributed equally between the head-neck vessels and the descending aorta. This methodology will be extended to the hypoplastic heart surgeries where the cannulation has to be performed through ductus arterious due to the underdeveloped aorta anatomy, Figure 2. We also like to compute entire operating characteristics of these configurations (close to 30 individual CFD runs at different operating configurations for each patient-specific model). Embryonic Aortic Arch Development: Casts of the embryonic aortic arches are dissected from White Leghorn Eggs (at different developmental Hamburger-Hamilton stage) under fluorescent microscope and scanned with Micro-CT in order to reconstruct the 3D aortic arch anatomy. The flow domain inside the aortic arches is discretized with 500,000 tetrahedral elements using Gambit (Ansys Inc.). As an ongoing study [16], the aforementioned pulsatile 2nd Order CFD solver is employed to calculate mesh independent solution for each model representing a different developmental stage (close to 10 different development stages). Flow split boundary conditions are used at the outlets distributing the total cardiac output to dorsal aorta and cranial vessels with a ratio of 90/10. Pulsatile flow waveforms from the literature are used for each stage as plug-flow inflow boundary conditions [17]. Cyber-enabled Pre-Surgical Cardiovascular Planning: Current attempt towards the cyber-enaled pre-surgical cardiovascular planning is to translate the complex patient-specific, time-critical three-dimensional (3D) actions of the surgeon to the subsequent CFD analysis. The state-of-art human-shape sketching beacon developed by our group will enable the generation of the complex, experience driven inventions of the surgeon and evaluating their quantitative effect on flow dynamics. The current emphasis is given towards the coronary artery bypass grafts (CARBG) with 10 different surgical configurations. Preliminary Results Pediatric Cannulation: Hemodynamic parameters describing the pulsatile energetics, pressure drop, perfusion, wall shear stress and blood damage index are calculated for the CPB model. The high-speed canulla jet flow and its stagnation on the aortic wall contributed to the reduced flow pulsaility in the head neck vessels which relates to the poor cerebral perfusion observed during CBP [18]. Wall shear and hemolysis index values appear above the physiological limits which prominently demands extensive design optimization on pediatric cannulation. Concluding Remarks and Future Directions: Pediatric Cannulation: As identified in our previous study [1] drastic hemodynamic differences and intense biophysical loading of the pathological CPB configuration necessitates urgent bioengineering improvements in cannula design, perfusion flow waveform and configuration. Hence, the validated CFD model will serve as a valuable tool to document the baseline condition for different congenital disease states and a key tool for CPB cannula design and optimization. Coupled to a lumped parameter model the 3D hemodynamic characteristics will aid the surgical decision making process of the perfusion strategies in complex congenital heart surgeries. Embryonic Chick Aortic Arch: As an initial attempt to investigate and quantify the hemodynamic and anatomical changes in the aortic arch over the course of entire developmental timeline this study can be correlated with morphodynamic studies and existing gene/protein expression patterns. The proposed simulations will be used to characterize alterations in fluid dynamics, associated with cardiac development which is critical for defining the mechanism responsible for clinically prevalent heart defects. Cyber-enabled Pre-Surgical Cardiovascular Planning: The proposed virtual surgical prediction/optimization study will aid the surgical decision making process and once clinically implemented will reduce the cardiopulmonary by-pass time, improve hemodynamic outcome and eliminate trial-error during complex cardiac surgeries. In conclusion based on the growing needs of our cutting-edge research we are looking for high computing power which is beyond the limits of that is currently eligible through our university. References: 1. Pekkan K, Dur O, Kanter K, Sundareswaran K, Fogel M, Yoganathan A, Undar A, Neonatal Aortic Arch Hemodynamics and Perfusion during Cardiopulmonary Bypass, Journal of Biomechanical Engineering, in 2nd revision, 2008 2. Pekkan K., Dasi LP, Nourparvar P, Yerneni S, Tobita K, Fogel MA, Keller B, Yoganathan A, In Vitro Hemodynamic Investigation of the Embryonic Aortic Arch at Late Gestation, Journal of Biomechanics, accepted, 2008. 3. Wang C, Pekkan K, de Zlicourt D, Parihar A, Kulkarni A, Horner M, Yoganathan AP, Progress in the CFD Modeling of Flow Instability in Anatomical Total Cavopulmonary Connections, accepted, Annals of Biomedical Engineering, Nov;35(11):1840-56, 2007. (Results featured on the cover illustration) 4. Groenendijk BC, Van der Heiden K, Hierck BP, Poelmann RE. The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model. Physiology. 2007 Dec;22:380-9. 5. Raghavan M.L., Kratzberg, J., Castro de Tolosa, E.M., Hanaoka, M.M., Walker, P. and da Silva, E.S., Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm. J Biomech, 2005. 6. Li Z. and Kleinstreuer, C., Fluid-structure interaction effects on sac-blood pressure and wall stress in a stented aneurysm. J Biomech Eng, 2005. 127(4): p. 662-71. 7. Vsrghese, S., and Frankel, S., 2003, Numerical Modeling of Pulsatile Turbulent Flow in a Stenosed Tube, ASME J. Biomech. Eng,. 126, pp. 625-635. 8. Toriia, R., Wooda, N. B., Hughesb, A. D., Thomb, S. A., Aguado-Sierrac, J., Daviesb, J. E., Francisb, D. P., Parkerc, K. H., and Xua, X. Y., 2007, "A computational study on the influence of catheter-delivered intravascular probes on blood flow in a coronary artery model," Journal of Biomechanics, in press. 9. de Zelicourt D.A., Pekkan, K.,Parks, J.,Kanter, K.,Fogel, M.,Yoganathan, A. P., Flow study of an extracardiac connection with persistent left superior vena cava. J Thorac Cardiovasc Surg, 2006. 131(4): p. 785-91. 10. Pekkan K., Kitajima, H.D., de Zelicourt, D., Forbess, J.M., Parks, W.J., Fogel, M.A., Sharma, S., Kanter, K.R., Frakes, D. and Yoganathan, A.P., Total cavopulmonary connection flow with functional left pulmonary artery steno angioplasty and fenestration in vitro. Circulation, 2005. 112(21): p. 3264-71. 11. Ungerleider, R. M., 2005, "Practice Patterns in Neonatal Cardiopulmonary Bypass," Asaio J, 51(6), pp. 813-815. 12. Papantchev V, H. S., Todorova D, Naydenov E, Paloff A, Nikolov D,, and Tschirkov A, O. W., 2007, "Some variations of the circle of Willis, important for cerebral protection in aortic surgery - a study in Eastern Europeans," Eur J Cardiothorac Surg., 31(6), pp. 982-989. 13. Schumacher, J., Eichler, W., Heringlake, M., Sievers, H. H., and Klotz, K. F., 2004, "Intercompartmental fluid volume shifts during cardiopulmonary bypass measured by A-mode ultrasonography," Perfusion, 19(5), pp. 277-281. 14. Undar, A., Vaughn, W. K., and Calhoon, J. H., 2000, "The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model," 15, pp. 121-128. 15. Hogers, B., DeRuiter, M. C., Baasten, A. M., Gittenberger-de Groot, A. C., and Poelmann, R. E., 1995, "Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo," Circulation research, 76(5), pp. 871-877. 16. Yajuan Wang, Onur Dur, Michael J. Patrick, Joseph P. Tinney, Kimimasa Tobita, Kerem Pekkan, Bradley B. Keller.Hemodynamic Investigation of Normal Developing Aortic Arch in the Chick Aortic Arch in the Chick Embryo, Bypass. ASME Summer Conference 2008 17. Hu N, Clark EB. Hemodynamics of the stage 12 to stage 29 chick embryo. Circ Res. 1989 Dec;65(6):1665-70. 18. Undar, A., Vaughn, W. K., and Calhoon, J. H. The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model, 2000, 15, pp. 121-128.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：我们计算流体动力学 (CFD) 研究的目标是 i) 优化新生儿/儿童体外循环 (CPB) 期间儿科插管技术的方向和设计，特别是我们希望将我们当前的工作 [1] 扩展到复杂的领域主动脉弓发育不良综合征的重建手术 ii) 研究血流驱动的血流动力学负荷对主动脉弓发育的作用（异常负荷条件可能导致复杂的心脏缺陷）[2,4] (iii)在复杂的重建手术中推进和实现网络支持的术前心血管规划。简介和研究目的：结合解剖数据的精确重建（通过 MRI、血管造影、超声心动图和 CT），CFD 模拟技术已越来越被认为是心血管系统的手术规划工具。示例研究包括腹主动脉瘤 [5-6]、动脉狭窄 [7]、冠状动脉 [8] 和先天性心脏病 (CHD) [9,10]。目前，此类患者特定建模 CFD 应用的研究兴趣已从分析转向系统几何优化，并且需要高性能计算能力。为了说明问题的范围，标准瞬态解剖 3D CFD 结果 (n=1) 中的典型数字需要约 125Gb 的存储空间来存储原始数据（以及单 PI 16 节点集群中约 1 周的 CPU 时间）可以考虑。对于每个解剖重建，需要 15 个这样的解决方案，通常针对三个心输出量。仅此 CFD 建模工作的原始数据就需要约 2.4TB 的临时和永久数据存储系统。参考我们的第一个研究目标，儿科插管是复杂先天性心脏缺陷阶段性姑息治疗的关键要素，需要在生命早期进行心脏直视手术。这些每年影响 20,000 名儿童的手术通常需要长时间的体外循环 (CPB)。众所周知，标准 CPB 技术对新生儿 [11] 非常有害，包括较高的炎症风险、早产威利斯环 [12]、不平衡、非生理性器官灌注 [13, 14]，导致暂时或永久性脑损伤高达 25 % 的患者。因此，迫切需要优化儿科/新生儿体外循环回路组件的生物力学设计，该回路组件面临复杂的脉动和空化流的挑战，必须针对患者特定的解剖和生理学进行定制。我们的第二个研究目标是调查血流驱动的血流动力学负荷，解决主动脉弓发育中的形式与血流关系。尽管通过系统的体内血流可视化研究已证实改变（异常）的静脉血流模式是冠心病的主要原因[15]，但工程流体动力学分析工具最近得到了发展，以支持这些观察结果的量化。从本质上讲，心脏发育过程中这些血流变化的量化对于确定临床上常见的心脏缺陷（每 100 名儿童中就有 1 名）的机制以及优化其宫内和产后管理至关重要。最近，我们的团队还开始尝试通过使用计算机辅助工具在诊所或床边虚拟修改和优化解剖 MRI 重建并使用 CFD 模拟血流来实现网络化的术前心血管计划。所提出的方法如图 1 所示。尖端的高性能计算对于该过程的所有步骤（即预处理、求解器和后处理）再次至关重要。由于术前临床决策将基于每位患者至少约 10 个不同的候选参数解剖结构，因此仅此 CFD 建模工作的总行数据就需要约 24TB 的存储空间。尽管为单个患者生成的 CFD 数据量相当大，并且目前实际上无法常规访问，但进行这项工作对患者的健康有明显的好处。在临床上，这相当于生活质量的提高、心输出量的增加和运动耐量的提高。示例方法：儿科 CPB：通过夹紧升主动脉并插入计算机辅助设计模型，对具有正常主动脉弓的儿科患者（年龄：12.5，BSA：1.32m2）进行 3D 心脏 MRI 重建，创建虚拟 CPB 10Fr 锥形通用插管。插管和主动脉弓相互定向，以模拟典型的标准儿科 CPB 配置。脉动 3D 血流速度和压力是使用商业计算流体动力学 (CFD) 软件（Fluent，ANSYS Inc.）使用经过实验验证的二阶精确求解器来计算的 [3]。通过同时调用 20 个节点（每个节点均配备 3.2 GHz 32 位 Intel Pentium4 处理器），在并行 Linux 集群上执行模拟。模拟三个收敛周期（周期为 0.635 秒）的计算大约需要 72 小时。插管入口流量波形是根据体内 PC-MRI 和仔猪动物模型生理实验（使用 DLP75010 插管）测量的，均匀分布在头颈血管和降主动脉之间。这种方法将扩展到发育不全的心脏手术，由于主动脉解剖结构不发达，插管必须通过动脉导管进行，图 2。我们还喜欢计算这些配置的整个操作特性（在不同的条件下进行了近 30 次单独的 CFD 运行）。每个患者特定型号的操作配置）。胚胎主动脉弓发育：在荧光显微镜下从白来亨蛋（处于不同发育的汉堡汉密尔顿阶段）解剖胚胎主动脉弓的铸件，并使用 Micro-CT 扫描，以重建 3D 主动脉弓解剖结构。使用 Gambit (Ansys Inc.) 使用 500,000 个四面体单元对主动脉弓内的流域进行离散化。作为一项正在进行的研究 [16]，上述脉冲二阶 CFD 求解器用于计算代表不同发展阶段（接近 10 个不同发展阶段）的每个模型的网格独立解。在出口处使用流分流边界条件，将总心输出量以 90/10 的比例分配到背主动脉和颅血管。文献中的脉动流波形用于每个阶段作为活塞流流入边界条件[17]。网络化的术前心血管规划：当前对网络化的术前心血管规划的尝试是将外科医生复杂的患者特定、时间关键的三维 (3D) 操作转化为后续的 CFD 分析。我们团队开发的最先进的人形素描信标将使外科医生能够生成复杂的、经验驱动的发明，并评估它们对流动动力学的定量影响。目前的重点是具有 10 种不同手术配置的冠状动脉旁路移植术 (CARBG)。初步结果 儿科插管：针对 CPB 模型计算描述脉动能量、压降、灌注、壁剪切应力和血液损伤指数的血流动力学参数。高速套管射流及其在主动脉壁上的停滞导致头颈血管中的血流脉动减少，这与 CBP 期间观察到的脑灌注不良有关[18]。壁剪切力和溶血指数值高于生理极限，这突出需要对儿科插管进行广泛的设计优化。结束语和未来方向：儿科插管：正如我们之前的研究 [1] 所确定的，病理性 CPB 配置的巨大血流动力学差异和强烈的生物物理负荷需要在插管设计、灌注流波形和配置方面进行紧急生物工程改进。因此，经过验证的 CFD 模型将成为记录不同先天性疾病状态基线状况的宝贵工具，也是 CPB 插管设计和优化的关键工具。与集中参数模型相结合，3D 血流动力学特征将有助于复杂先天性心脏病手术中灌注策略的手术决策过程。胚胎鸡主动脉弓：作为研究和量化主动脉弓在整个发育时间线过程中的血流动力学和解剖学变化的初步尝试，这项研究可以与形态动力学研究和现有基因/蛋白质表达模式相关联。所提出的模拟将用于表征与心脏发育相关的流体动力学的变化，这对于定义临床上普遍的心脏缺陷的机制至关重要。网络支持的术前心血管规划：拟议的虚拟手术预测/优化研究将有助于手术决策过程，一旦临床实施，将减少心肺转流时间，改善血流动力学结果并消除复杂心脏手术期间的试验错误。总之，基于我们尖端研究不断增长的需求，我们正在寻找超出我们大学当前资格限制的高计算能力。参考文献： 1. 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