Multiscale Model of Ascending Thoracic Aortic Aneurysm

升胸主动脉瘤的多尺度模型

• 批准号: 10181130
• 负责人: VICTOR H BAROCAS
• 金额: $ 17.95万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10181130
• 关键词: Accounting; Actins; Aneurysm; Aorta; Architecture; Behavior; Cadaver; Caliber; Cells; Cessation of life; Clinical; Clinical Data; Collagen; Collagen Fiber; Complex; Computer Models; Coronary Vessels; Coupled; Cytoskeleton; Dangerousness; Data; Data Set; Deposition; Dilatation - action; Dissection; Elastin; Elements; Environment; Evaluation; Event; Evolution; Excision; Extracellular Matrix; FBN1; Failure; Feedback; Fiber; Filament; Geometry; Goals; Growth; Health; Heart; Individual; Laws; Lead; Life; MRI Scans; Measurement; Mechanics; Medial; Methods; Modeling; Nature; Operative Surgical Procedures; Outcome; Patients; Physiological; Process; Property; Risk; Risk Assessment; Role; Rupture; Shapes; Smooth Muscle Myocytes; Specific qualifier value; Stretching; Structure; Testing; Thoracic Aortic Aneurysm; Thoracic aorta; Time; Tissue Model; Tissue Sample; Tissues; Translating; Tunica Adventitia; Vascular System; Vascular remodeling; Work; X-Ray Computed Tomography; animal tissue; aortic valve; ascending aorta; base; cell growth; cost; density; driving force; experimental study; insight; materials science; mechanical behavior; mechanical properties; mortality risk; multi-scale modeling; next generation; novel; outcome forecast; predictive modeling; predictive tools; pressure; repaired; response; tissue stress; tool

Thoracic aortic aneurysms, a majority of which occur in the ascending aorta, have significant mortality risk and are thus a major health concern. The primary risk in ascending thoracic aortic aneurysm (aTAA) is that of aortic dissection (splitting the aortic wall) with subsequent damage to coronary vessels and/or the aortic valve, or possibly rupture of the aorta itself. Surgical repair has its own risks, and the current state of the art, based on correlation between aTAA diameter and likelihood of rupture, is statistical, meaning that some patients who do not have surgery die from aneurysm complications, and others undergo a dangerous surgery when conservative treatment would suffice. For better risk assessment, we must understand what features of an aneurysm (or a pre-aneurysmal dilatation) are most threatening. We propose to develop a predictive, multiscale model of the remodeling, dissection, and possible rupture of an aTAA. The model will bridge two scales: the (continuous) vessel scale, capturing the gross shape of the aneurysm, and the (discrete) cell/lamellar scale, accounting for elastin and collagen in an elastic lamella of the vessel wall, an idealized smooth muscle cell, and interlamellar connections. The mechanical response of these small-scale elements will be fully coupled to the macroscopic scale. Because the microscale model will treat individual elements separately and structurally, we will be able to impose more complex and realistic remodeling rules than current continuous, constrained-mixture models. For example, we will be able to introduce collagen deposition by the smooth muscle cells based on the stretch of cytoskeletal elements, we will be able to degrade individual collagen fibers rather than introducing treating the problem in terms of a mass density, and we will be able to account for complex deformations that arise from the non-cylindrical geometry of the aTAA. This approach is the natural and necessary next generation following on the last three to four decades of continuum-level remodeling laws. The multiscale model will be parameterized by comparing model results to the experimental data, and once properly specified, the model will be used to generate and test hypotheses about the nature of aTAA growth and rupture, such as exploring the specific role of interlamellar connections or different possible remodeling rules. This project will provide new insight into the mechanisms by which aTAA’s grow and fail, and it will also serve as a potential paradigm for other studies of remodeling in the vascular system and beyond.

胸主动脉瘤大部分发生在升主动脉，具有显着的临床意义。 死亡风险，因此是一个主要的健康问题。胸主动脉升主动脉的主要风险 动脉瘤 (aTAA) 是指主动脉夹层（主动脉壁裂开）并随后造成的损伤 冠状血管和/或主动脉瓣，或主动脉本身可能破裂。手术修复有 基于 aTAA 直径和 破裂的可能性是统计性的，这意味着一些未接受手术的患者会死于 动脉瘤并发症，以及其他人在保守治疗时接受危险的手术 就足够了。为了更好地评估风险，我们必须了解动脉瘤（或 动脉瘤前扩张）是最具威胁性的。我们建议开发一个预测性的、 aTAA 重塑、解剖和可能破裂的多尺度模型。这 模型将连接两个尺度：（连续）容器尺度，捕捉容器的总体形状 动脉瘤和（离散）细胞/层状鳞片，解释了弹性体中的弹性蛋白和胶原蛋白 血管壁板层、理想化的平滑肌细胞和层间连接。这 这些小尺度元素的机械响应将完全耦合到宏观尺度。 由于微尺度模型将在结构上分别处理各个元素，因此我们 将能够施加比当前连续的更复杂和更现实的重塑规则， 约束混合模型。例如，我们将能够通过以下方式引入胶原蛋白沉积： 基于细胞骨架元素拉伸的平滑肌细胞，我们将能够降解 单个胶原纤维而不是引入质量密度来解决问题， 我们将能够解释由非圆柱体引起的复杂变形 aTAA 的几何形状。这种方法是下一代自然和必要的 过去三到四十年的连续体水平重塑定律。 通过将模型结果与实验结果进行比较来对多尺度模型进行参数化 数据，一旦正确指定，该模型将用于生成和测试有关的假设 aTAA生长和破裂的本质，例如探索层间的具体作用 连接或不同的可能的重塑规则。该项目将提供新的见解 aTAA 成长和失败的机制，它也将作为一个潜在的 血管系统及其他重塑的其他研究的范例。