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

基本信息

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
项目类别：
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

项目摘要

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 (CA) 是由于局部壁弱化和脑动脉外翻引起的扩张。适应不良的重塑。虽然破裂相对罕见，但破裂后存活率较低，原因是血管痉挛和中风等并发症。由于大多数脑动脉瘤是稳定的，因此能够预测破裂既可以进行早期干预，又可以消除不必要的外科手术以稳定病情动脉瘤。为了预测破裂，已经开发了许多计算模型与临床可测量因素的相关性，例如动脉瘤形状或血流动力学。但是，这些模型还不够准确，无法用于临床。目前的一个主要缺点方法是它不考虑复杂的破裂机制，而是试图从形状上跳跃和/或流体动力学直接影响破裂风险。相反，我们将建立在对机械的理解之上异质性及其在组织生长、重塑和衰竭中的作用。通过将异质性纳入通过对 CA 的描述，我们将为未来的模型提供信息，并能够更准确地评估 CA 破裂风险。我们假设脑动脉瘤在机械上具有异质性，并且这种异质性是可预测的动脉瘤的破裂可能性。我们进一步假设材料异质性可以是由 (i) 动脉瘤中血流引起的壁剪切应力场和 (ii) 的几何形状确定动脉瘤，这两者都可以在临床环境中确定。我们提出了一系列新颖的实验和计算模型，旨在阐明组织的作用脑动脉瘤生长、重塑和破裂的异质性。使用新鲜切除的人体动脉瘤组织，我们将测量区域组织尺度的机械特性、ECM 结构和成分、细胞组织和动脉瘤的破裂应力。接下来，我们将开发并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，我们将使用对动脉瘤内的结构和血流力学进行计算分析，以连接这些临床可测量的指标到临床不可测量的材料特性。这项研究的结果将提供推进脑动脉瘤破裂预测模型所需的关键机制见解。