Hemodynamic Intervention of Intracranial Aneurysms

描述(申请人提供)：血流动力学干预是治疗颅内动脉瘤的一种很有前途的血管内治疗方法。然而，对现实中的动脉瘤对这种干预的血流动力学和生物学反应知之甚少。了解血流动力学和生物反应之间的相互作用对于提高动脉瘤治疗的成功率至关重要。我们假设冲击血流的破坏将导致良好的动脉瘤样壁重塑和颅内动脉瘤的血栓闭塞。我们结合了活体兔模型和基于图像的计算流体动力学方法来验证这一假说，具体目标如下：1)量化支架置入对真实动脉瘤几何形状的血流动力学影响；2)确定减少的壁切应力对动脉瘤生长的影响；3)确定减少的壁切应力对血管重塑因子的影响；以及4)开发血管内假体以改变动脉瘤内的流动，使其进入以回流区和长颗粒滞留时间为特征的血栓形成环境。科学意义：定量了解导致动脉瘤病理发生有利变化的血流动力学因素将有助于开发更有效的治疗方案。该奖项的总体目标是让流体力学领域的一位知名量化科学家和工程师过渡到一名在生物工程、定量血管生物学以及脑血管疾病和治疗过渡研究方面具有专长的定量生物医学研究员。提出了一个多方面的计划，在翻译性神经血管干预、综合脑血管生物学和医学成像领域进行培训。

DESCRIPTION (provided by applicant): Hemodynamic intervention is a promising endovascular treatment for intracranial aneurysms. However, little is known about hemodynamic and biological responses of realistic aneurysms to such intervention. Understanding the interaction between the blood flow dynamics and biological response is vital to improving the success of aneurysm treatments. We hypothesize that disruption of impacting flow will induce favorable aneurysmal wall remodeling and thrombotic occlusion of intracranial aneurysms. We combine an in vivo rabbit model and imaged-based computational fluid dynamics approach to test this hypothesis by addressing the following Specific Aims: 1) to quantify the hemodynamic effects of stenting in realistic aneurysm geometries; 2) to determine the effects of reduced wall shear stress on aneurysm growth; 3) to determine the effect of reduced wall shear stress on vascular remodeling factors; and 4) to develop endovascular prostheses to modify intra-aneurysmal flow into a thrombogenetic environment characterized by recirculation zones and long particle residence time. Scientific Significance: Quantitative understanding of the hemodynamic factors that induce favorable changes in the aneurysm pathology will help develop more effective treatment paradigms. The overall goal of this Award is for a well-established quantitative scientist and engineer in the area of fluid mechanics to make a career transition to a quantitative biomedical researcher with expertise in bioengineering, quantitative vascular biology, and transitional research on cerebrovascular disease and therapy. A multi-faceted plan is proposed to train in areas of translational neurovascular intervention, integrative cerebrovascular biology and medical imaging.