Hemodynamic Intervention of Intracranial Aneurysms

描述（申请人提供）：血流动力学介入治疗是一种很有前途的颅内动脉瘤的血管内治疗方法。然而，对于这种干预对于真实动脉瘤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。我们假设冲击流的中断将诱导有利的动脉瘤壁重塑和颅内动脉瘤的血栓闭塞。我们结合了兔体内模型和基于图像的计算流体动力学方法，通过解决以下具体目标来验证这一假设：1)量化支架植入在现实动脉瘤几何形状中的血流动力学效应；2)确定减小壁面剪应力对动脉瘤生长的影响；3)确定减小壁面剪应力对血管重构因子的影响；4)开发血管内假体，改变动脉瘤内血流，使其形成以再循环区和长颗粒停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有利变化的血流动力学因素将有助于开发更有效的治疗范例。该奖项的总体目标是为流体力学领域的成熟的定量科学家和工程师提供职业过渡到具有生物工程，定量血管生物学和脑血管疾病和治疗过渡研究专业知识的定量生物医学研究人员。提出了一个多方面的计划，在转化神经血管干预，综合脑血管生物学和医学成像领域的培训。

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.