Multiscale Model of Ascending Thoracic Aortic Aneurysm

胸主动脉瘤，其中大部分发生在升主动脉，有显著的 死亡风险很大，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 主动脉瘤(Ataa)是指主动脉夹层(使主动脉壁破裂)，继而对 冠状动脉和/或主动脉瓣，或可能的主动脉本身破裂。外科修复有 它自身的风险，以及基于Ataa Diameter和Ataa Diameter之间的相关性的当前技术状态 破裂的可能性是统计的，这意味着一些没有做手术的患者死于 动脉瘤并发症，以及其他保守治疗时接受危险手术 就足够了。为了更好地评估风险，我们必须了解动脉瘤的哪些特征(或 动脉瘤前扩张)是最具威胁性的。我们建议开发一种可预测的、 重建、解剖和可能破裂的Ataa的多尺度模型。这个 模型将跨越两个比例：(连续的)血管比例，捕捉到 动脉瘤，以及(离散的)细胞/板层鳞片，说明弹性蛋白和胶原蛋白 管壁的板层、理想化的平滑肌细胞和板层间的连接。这个 这些小尺度单元的力学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对待单个元素，因此我们 将能够实施比目前连续的、更现实的重塑规则， 约束混合模型。例如，我们将能够通过 平滑肌细胞基于细胞骨架元素的伸展，我们将能够降解 单独的胶原纤维而不是引入质量密度来治疗问题， 我们将能够解释由非圆柱体引起的复杂变形 阿塔亚的几何学。这种方法是下一代自然和必要的 关于过去三四十年的连续体水平重塑规律。 通过将模型结果与实验结果进行比较，多尺度模型将被参数化 数据，一旦正确指定，该模型将被用来生成和测试关于 Ataa生长和破裂的本质，如探索板层间的具体作用 连接或不同可能的重塑规则。该项目将提供新的洞察力 Ataa的成长和失败的机制，它也将作为一个潜在的 血管系统及其他重塑研究的范例。

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.