VASCULAR FUNCTION BY MAGNETIC RESONANCE ANGIOGRAPHY

目前尚不清楚为什么有动脉粥样硬化风险的人在某些血管床上会比其他血管床上的人患上更严重的疾病，例如，股动脉往往比臂动脉更严重。我们假设这些不同的易感性与这些个体内血管内皮细胞功能的区域差异有关。壁面切应力被认为是血管内皮细胞活性的主要血流动力学刺激因素。因此，比较不同血管床的壁切应力刺激与内皮反应的关系可以评估内皮功能的区域差异。利用相位对比磁共振血管成像，我们已经显示了正常臂动脉反应性充血高峰时的壁切应力与由此导致的血管扩张之间的线性关系。我们还开发了另一种方法，通过评估缺血后充血后血管内皮细胞对壁切应力的调节时间过程来评估内皮刺激反应关系，并开发了一种评估单个动脉横断面内壁切应力周向分布的技术。该项目的目的是1)确定在存在心血管危险因素和血管疾病的情况下，内皮刺激-反应关系是否发生改变，2)确定在高脂血症受试者服用HMG-CoA还原酶抑制剂6周后，这些关系是否对内皮功能的变化敏感，以及3)确定这种关系或周向应力分布是否在不同的血管床上不同。研究人员预计，这项研究将提高区分内皮功能正常和受损的能力，并将加强对动脉粥样硬化发展的理解。该提案将涉及心血管临床研究专家和约翰霍普金斯大学几个世界知名部门的指导、培训和资源：心血管核磁共振、生物医学工程和公共卫生学院。导师、合作者、环境和研究计划是实现申请人的长期目标的理想选择，即成为一名独立的临床研究员，将创新的工程技术应用于以患者为导向的心血管问题。

It is unclear why individuals at risk for atherosclerosis develop more severe disease in some vascular beds than others, e.g. femoral arteries tend to develop much more severe disease than do brachial arteries. We hypothesize that these different susceptibilities are associated with regional differences in vascular endothelial function within those individuals. Wall shear stress is considered to be the primary hemodynamic stimulus for endothelial activity. Therefore, comparing the relationship between wall shear stress stimulus and endothelial response in different vascular beds may allow the evaluation of regional differences in endothelial function. Using phase-contrast magnetic resonance angiography, we have shown a linear relationship between wall shear stress during peak reactive hyperemia and resulting vessel dilatation in normal brachial arteries. We have also developed another method to assess endothelial stimulus response relationship by evaluating the time-course of endothelial regulation of wall shear stress following post-ischemic hyperemia, and a technique to assess circumferential distribution of wall shear stress in a single arterial cross-section. The aims of this project are 1) to determine whether the endothelial stimulus-response relationships are altered in the presence of cardiovascular risk factors and in the presence of vascular disease, 2) to determine whether the relationships are sensitive to changes in endothelial function after a 6-week course of an HMG-Co A reductase inhibitor in subjects with hyperlipidemia, and 3) to determine whether the relationships or the circumferential stress distribution differ in different vascular beds. The investigators anticipate that this study will improve the ability to distinguish between normal and impaired endothelial function, and will enhance the understanding of atherosclerosis development. The proposal will involve mentorship, training, and resources from cardiovascular clinical research experts and several world-renown divisions of Johns Hopkins: Cardiovascular MRI, Biomedical Engineering, and The School of Public Health. The mentors, collaborators, environment, and research plan are ideal for achieving the applicant's long-term goal of becoming an independent clinical investigator, applying innovative engineering techniques toward patient-oriented cardiovascular problems.