Multiscale Model of Ascending Thoracic Aortic Aneurysm

升胸主动脉瘤的多尺度模型

• 批准号: 10220118
• 负责人: VICTOR H BAROCAS
• 金额: $ 37.85万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220118
• 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; Prognosis; 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; 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，其中大部分发生在升主动脉，具有显著的 死亡风险，因此是一个主要的健康问题。升胸主动脉的主要风险 动脉瘤（aTAA）是主动脉夹层（主动脉壁裂开），随后损害 冠状血管和/或主动脉瓣，或可能主动脉本身破裂。手术修复有 基于aTAA直径与 破裂的可能性是统计学上的，这意味着一些没有手术的患者死于 动脉瘤并发症，还有人在保守治疗时经历了危险的手术 就足够了为了更好地进行风险评估，我们必须了解动脉瘤（或 动脉瘤前扩张）是最危险的。我们建议开发一个预测性的， aTAA重塑、夹层和可能破裂的多尺度模型。的 模型将桥接两个尺度：（连续）血管尺度，捕捉血管的总体形状。 动脉瘤，和（离散）细胞/层状规模，占弹性蛋白和胶原蛋白在弹性 血管壁的板层、理想化的平滑肌细胞和板层间连接。的 这些小尺度元件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单独处理各个元素， 将能够施加比当前连续更复杂和现实的重塑规则， 约束混合模型例如，我们将能够引入胶原蛋白沉积， 平滑肌细胞的基础上伸展的细胞骨架元素，我们将能够降解 单独的胶原纤维而不是引入根据质量密度来处理问题， 我们就能解释非圆柱体产生的复杂变形 aTAA的几何形状。这种方法是自然和必要的下一代以下 在过去的三到四十年里，连续水平的重塑法律。 将通过比较模型结果与实验结果来参数化多尺度模型。 数据，一旦适当指定，模型将用于生成和测试假设， aTAA生长和断裂的性质，如探索层间 连接或不同的可能的重塑规则。该项目将提供新的见解， aTAA的生长和失败的机制，它也将作为一个潜在的 为血管系统及其他领域重塑的其他研究提供了范例。

项目成果

Ex Vivo Mechanical Tests and Multiscale Computational Modeling Highlight the Importance of Intramural Shear Stress in Ascending Thoracic Aortic Aneurysms.

离体机械测试和多尺度计算模型强调了壁内剪切应力在升胸主动脉瘤中的重要性。

• DOI: 10.1115/1.4045270
• 发表时间: 2019
• 期刊: Journal of biomechanical engineering
• 作者: Korenczuk,ChristopherE;Dhume,RohitY;Liao,KennethK;Barocas,VictorH
• 通讯作者: Barocas,VictorH

A structural bio-chemo-mechanical model for vascular smooth muscle cell traction force microscopy.

• DOI: 10.1007/s10237-023-01713-6
• 发表时间: 2023-08
• 期刊: BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
• 影响因子: 3.5
• 作者: Flanary, Shannon M.;Barocas, Victor H.
• 通讯作者: Barocas, Victor H.

Statistical shape representation of the thoracic aorta: accounting for major branches of the aortic arch.

胸主动脉的统计形状表示：考虑主动脉弓的主要分支。

• DOI: 10.1080/10255842.2022.2128672
• 发表时间: 2023
• 期刊: Computer methods in biomechanics and biomedical engineering
• 影响因子: 1.6
• 作者: Wiputra,Hadi;Matsumoto,Shion;Wagenseil,JessicaE;Braverman,AlanC;Voeller,RochusK;Barocas,VictorH
• 通讯作者: Barocas,VictorH

The Ring-Pull Assay for Mechanical Properties of Fibrous Soft Tissues - An Analysis of the Uniaxial Approximation and a Correction for Nonlinear Thick-Walled Tissues.

• DOI: 10.1007/s11340-020-00623-3
• 发表时间: 2021-01
• 期刊: Experimental mechanics
• 影响因子: 2.4
• 作者: Mahutga RR;Schoephoerster CT;Barocas VH
• 通讯作者: Barocas VH

A Hybrid Microstructural-Continuum Multiscale Approach for Modeling Hyperelastic Fibrous Soft Tissue.

• DOI: 10.1007/s10659-021-09843-7
• 发表时间: 2021-08
• 期刊: JOURNAL OF ELASTICITY
• 影响因子: 2
• 作者: Nikpasand, Maryam;Mahutga, Ryan R.;Bersie-Larson, Lauren M.;Gacek, Elizabeth;Barocas, Victor H.
• 通讯作者: Barocas, Victor H.