Role of mechanical heterogeneity in cerebral aneurysm growth and rupture

机械异质性在脑动脉瘤生长和破裂中的作用

• 批准号: 10585539
• 负责人: PATRICK W ALFORD
• 金额: $ 52.29万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585539
• 关键词: Address; Aneurysm; Architecture; Arteries; Behavior; Biophysical Process; Blood flow; Brain; Brain Death; Brain Injuries; Cadaver; Cells; Cerebral Aneurysm; Circle of Willis; Clinic; Clinical; Clinical Management; Clip; Collagen; Complex; Computer Analysis; Computer Models; Early Intervention; Experimental Models; Extracellular Matrix; Failure; Future; Geometry; Growth; Heterogeneity; Human; Intervention; Invaded; Liquid substance; Macrophage; Maps; Measurable; Measures; Mechanics; Mediating; Methods; Modeling; Morphology; Operative Surgical Procedures; Patients; Process; Property; Risk; Role; Rupture; Ruptured Aneurysm; Sample Size; Sampling; Scanning; Series; Shapes; Stress; Stroke; Structure; Survival Rate; Testing; Theoretical model; Time; Tissue Donors; Tissues; Unnecessary Surgery; Vasospasm; cerebral artery; extracellular; global environment; in vivo; insight; mechanical behavior; mechanical properties; next generation; novel; predictive modeling; predictive tools; pressure; repaired; shear stress; tool development

Cerebral aneurysms (CAs) are out-pouching dilations of cerebral arteries caused by local wall weakening and maladaptive remodeling. Though rupture is relatively rare, the post-rupture survival rate is low, due to complications such as vasospasm and stroke. Since the majority of cerebral aneurysms are stable, the ability to predict rupture would both allow early intervention and eliminate unnecessary surgical procedures for stable aneurysms. Many computational models have been developed with the aim of predicting rupture based on correlation with clinically measurable factors, such as aneurysm shape or blood flow dynamics. But, these models are not yet accurate enough for them to have been used in the clinic. A major shortcoming of the current approach is that it does not consider the complex mechanics of rupture but instead tries to leap from shape and/or fluid dynamics directly to rupture risk. In contrast, we will build on our understanding of mechanical heterogeneity and its role in tissue growth, remodeling, and failure. By incorporating heterogeneity into the description of the CA, we will inform future models and enable more accurate assessment of CA rupture risk. We hypothesize that cerebral aneurysms are mechanically heterogeneous, and this heterogeneity is predictive of the rupture potential of the aneurysm. We further hypothesize that the material heterogeneity can be determined from (i) the wall shear stress field caused by blood flow in the aneurysm and (ii) the geometry of aneurysm, both of which can be determined in a clinical setting. We propose a series of novel experiments and computational models aimed at elucidating the role of tissue heterogeneity on cerebral aneurysm growth, remodeling, and rupture. Using freshly excised human aneurysm tissue, we will measure regional tissue-scale mechanical properties, ECM structure and composition, cell organization, and the rupture stress of the aneurysm. Next, we will develop and use computational models to elucidate the biophysical mechanisms that connect tissue properties to aneurysm rupture. Finally, we will use computational analyses of the architecture and blood flow mechanics within the aneurysm to connect these clinically-measurable metrics to clinically non-measurable material properties. The findings from this study will provide key mechanistic insights needed to advance cerebral aneurysm rupture prediction models.

脑动脉瘤（CAS）是由局部壁削弱和 适应不良的重塑。尽管破裂相对较少，但由于 血管痉挛和中风等并发症。由于大多数脑动脉瘤是稳定的，因此能够 预测破裂将允许早期干预并消除不必要的手术程序 动脉瘤。已经开发了许多计算模型，目的是根据 与临床可测量因素（例如动脉瘤形状或血流动力学）的相关性。但是，这些 模型还不够准确，无法在诊所中使用。电流的主要缺点 方法是它不考虑破裂的复杂机制，而是试图从形状跳跃 和/或流体动力学直接以破裂风险。相反，我们将基于对机械的理解 异质性及其在组织生长，重塑和衰竭中的作用。通过将异质性纳入 CA的描述，我们将为未来的模型提供信息，并可以更准确地评估CA破裂风险。 我们假设脑动脉瘤在机械上是异质的，并且这种异质性是预测性的 动脉瘤的破裂潜力。我们进一步假设材料异质性可以是 由（i）由动脉瘤中的血流引起的壁剪应力场和（ii）的几何形状 动脉瘤，两者都可以在临床环境中确定。 我们提出了一系列旨在阐明组织作用的新型实验和计算模型 脑动脉瘤生长，重塑和破裂的异质性。使用新鲜切除的人动脉瘤 组织，我们将测量区域组织尺度机械性能，ECM结构和组成，细胞 组织和动脉瘤的破裂应力。接下来，我们将开发和使用计算模型 阐明将组织特性与动脉瘤破裂联系起来的生物物理机制。最后，我们将使用 动脉瘤内建筑和血流力学的计算分析以连接这些 临床上可测量的指标属于临床上不可衡量的材料特性。这项研究的发现将 提供推进脑动脉瘤破裂预测模型所需的关键机械见解。