MULTISCALE CARDIAC MODEL OF NANOPARTICLE-DRIVEN ATHEROSCLEROSIS

纳米颗粒驱动的动脉粥样硬化的多尺度心脏模型

• 批准号: 7601220
• 负责人: Daniel Richard Einstein
• 金额: $ 0.5万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601220
• 关键词: Acute; Algorithms; Arrhythmia; Arterial Fatty Streak; Atherosclerosis; Biochemistry; Biological; Biomechanics; Blood Circulation; Blood Viscosity; Cardiac; Cardiovascular Physiology; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Coronary; Data; Development; Elasticity; Endocardium; Endothelium; Epicardium; Exposure to; Foundations; Funding; Future; Goals; Grant; Heart; Heart Rate; Heart Valves; Image; In Situ; Individual; Inflammation; Inflammatory; Institution; Journals; Lead; Lesion; Link; Liquid substance; Magnetic Resonance Imaging; Manuscripts; Modeling; Mus; Particulate Matter; Pathology; Peer Review; Perfusion; Personal Satisfaction; Phase; Plant Roots; Progressive Disease; Publications; Research; Research Personnel; Resolution; Resources; Respiratory System; Respiratory physiology; Secondary to; Sedimentation process; Source; Technology; Three-Dimensional Image; Three-Dimensional Imaging; Time; United States National Institutes of Health; base; concept; cytokine; nanoparticle; pressure; respiratory; shear stress; size; success

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. With collaborators from PNNL: James Carson, Kevin Minard, Andrew Kuprat DATA SHARED to contribute to proposed grant This research is directed at generating the necessary preliminary data and the necessary computational technology to develop a multiscale computational model of the mouse heart that will link cardiovascular function to respiratory function. The ultimate goal is to investigate the relationship among atherosclerosis, the presence of nanoparticles, and the secondary perturbations of respiratory inflammation. Atherosclerosis is a progressive disease. However, there is growing evidence that acute exposure to ambient particulate matter may be involved in lesions of the coronary endothelium that lead to its onset. At the same time, it is well known that deleterious alterations in the fluid shear stress and coronary transmural pressure perturb endothelial biochemistry and exacerbate the local inflammation at the root of atherosclerotic plaque formation. Thus, the local dispersion and sedimentation of nanoparticles, the biomechanical alterations secondary to increased heart rate, altered blood viscosity and acute episodes of cardiac arrhythmia, and the release and circulation of inflammatory cytokines may act synergistically to promote atherosclerotic plaque formation. The long-term goal of this research is to investigate this synergy by linking cardiovascular function with respiratory function and biomechanics with biochemistry. During this phase of the project, we would like to acquire high-resolution (50 micron) images of a perfusion-fixed whole mouse, with the specific aim of carefully characterizing the geometry of the mouse heart in-situ, including coronary vasculature and cardiac valves. The data will used to develop a computable grid of the mouse heart that will serve as a foundation for future biophyics calculations related to cardiac function and pathology. Our current focus will be algorithm development for the completion of this task and is expected to result in a peer-reviewed publication. Our group has successfully developed computable grids from high-resolution MR images of the respiratory system as part of the NIH-funded NHLBI/BRP (1RO1HL073598-01A1 ) project entitled "3D Imaging and Computational Modeling of the Respiratory System". In addition, as part of the current project, we have successfully developed the technology for reconstructing mouse heart geometry from serial cryomicrotome images. Individual sections were nonlinearly registered (warped) to successive sections via a constrained elasticity based approach. The resulting volume has cellular resolution. In tandem, we have developed a scale-invariant gridding algorithm that quickly produces a quality, nearly orthogonal paving of biological geometries based on the concept of local feature size. It is now possible to automatically create three layers of excellent quality tetrahedra through the entire cardiac network. This is important as myofiber angles tend to organize in three layers (endocardium, mid-wall and epicardium). We are currently preparing two manuscripts based on this effort to be submitted to numerical journals. A third manuscript based on the application of the approach to the mouse heart data will be submitted later this year as the MR data becomes available. Thus, from a technological point of view, this project has a high chance of success. Finally, the collaborators on this project are experts in their field and have the necessary background to succesfully complete this project.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 与来自PNNL的合作者：James卡森，Kevin Minard，Andrew Kuprat 数据共享有助于拟议的赠款 本研究旨在生成必要的初步数据和必要的计算技术，以开发将心血管功能与呼吸功能联系起来的小鼠心脏多尺度计算模型。最终目标是研究动脉粥样硬化、纳米颗粒的存在和呼吸道炎症的继发性扰动之间的关系。动脉粥样硬化是一种进行性疾病。然而，越来越多的证据表明，急性暴露于环境颗粒物可能涉及冠状动脉内皮损伤，导致其发病。同时，众所周知，流体剪切应力和冠状动脉跨壁压的有害改变扰乱内皮生物化学并加剧动脉粥样硬化斑块形成根源处的局部炎症。因此，纳米颗粒的局部分散和沉降、继发于心率增加的生物力学改变、改变的血液粘度和心律失常的急性发作以及炎性细胞因子的释放和循环可协同作用以促进动脉粥样硬化斑块形成。本研究的长期目标是通过将心血管功能与呼吸功能以及生物力学与生物化学联系起来来研究这种协同作用。 在该项目的这一阶段，我们希望获得灌注固定的整个小鼠的高分辨率（50微米）图像，其具体目的是仔细表征小鼠心脏原位的几何形状，包括冠状血管和心脏瓣膜。这些数据将用于开发小鼠心脏的可计算网格，该网格将作为未来与心脏功能和病理学相关的生物物理学计算的基础。我们目前的重点将是完成这项任务的算法开发，预计将导致同行评审的出版物。 作为NIH资助的NHLBI/BRP（1 RO 1HL 073598 - 01 A1）项目“呼吸系统的3D成像和计算建模”的一部分，我们的团队已经成功地从呼吸系统的高分辨率MR图像开发了可计算网格。 此外，作为当前项目的一部分，我们已经成功地开发了从连续冷冻切片机图像重建小鼠心脏几何形状的技术。通过基于约束弹性的方法，将单个切片非线性配准（扭曲）到连续切片。所得体积具有细胞分辨率。在串联，我们已经开发了一个规模不变的网格算法，快速产生一个质量，近正交铺设的生物几何形状的基础上的概念，局部特征尺寸。现在可以通过整个心脏网络自动创建三层优质四面体。这一点很重要，因为肌纤维角倾向于组织成三层（内膜、中壁和心外膜）。我们目前正在准备两个手稿的基础上，这一努力将提交给数字期刊。第三份手稿的基础上的应用程序的方法，小鼠心脏数据将提交今年晚些时候作为MR数据变得可用。 因此，从技术角度来看，这个项目有很大的成功机会。 最后，这个项目的合作者都是各自领域的专家，并具有成功完成这个项目所需的背景。