Multiscale Model of Ascending Thoracic Aortic Aneurysm

升胸主动脉瘤的多尺度模型

基本信息

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
项目类别：
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

项目摘要

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.

胸腔主动脉瘤，大多数发生在上升主动脉中，具有显着死亡率风险，因此是主要的健康问题。上升胸主动脉的主要风险动脉瘤（ATAA）是主动脉夹层（裂开主动脉壁），随后损坏冠状血管和/或主动脉瓣，或主动脉本身可能破裂。手术修复已有其自身的风险以及基于ATAA直径与破裂的可能性是统计的，这意味着一些没有手术的患者死于保守治疗时，动脉瘤并发症，其他人进行危险手术会提供。为了获得更好的风险评估，我们必须了解动脉瘤的功能（或前动脉瘤的扩张）是最威胁性的。我们建议发展一种预测性， ATAA的重塑，解剖和可能破裂的多尺度模型。模型将桥接两个尺度：（连续的）血管刻度，捕获动脉瘤和（离散的）细胞/层状量表，弹性中的弹性蛋白和胶原蛋白容器壁的薄片，理想化的平滑肌细胞和层间连接。这些小型元素的机械响应将完全耦合到宏观尺度。因为微观模型将在结构上分别和结构处理各个元素，所以我们比当前连续的规则能够施加更复杂和现实的重塑规则，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范围，我们将能够降解单个胶原蛋白纤维，而不是引入质量密度来处理问题，而且我们将能够说明非圆柱形的复杂变形 ATAA的几何形状。这种方法是自然而必要的下一代之后在过去的三到四十年中，连续级别的重塑法律。多尺度模型将通过将模型结果与实验结果进行参数化。数据，一旦正确指定，该模型将用于生成和检验有关的假设 ATAA生长和破裂的性质，例如探索层间的特定作用连接或不同可能的重塑规则。该项目将为您提供新的见解 ATAA增长和失败的机制，这也将作为潜力用于血管系统及以后重塑的其他重塑研究的范例。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
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

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.

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.