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个体在某些血管床上比其他血管床上发展更严重的疾病，例如，股动脉往往比肱动脉发展更严重的疾病。我们假设这些不同的易感性与这些个体血管内皮功能的区域差异有关。壁面剪切应力被认为是内皮细胞活动的主要血流动力学刺激。因此，比较不同血管床壁面剪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。使用相对比磁共振血管造影，我们显示了在反应性充血高峰时壁剪切应力与正常肱动脉血管扩张之间的线性关系。我们还开发了另一种方法，通过评估缺血充血后血管壁剪切应力的内皮调节的时间过程来评估内皮刺激反应关系，并开发了一种在单一动脉横截面上评估血管壁剪切应力周向分布的技术。本项目的目的是：1)确定在存在心血管危险因素和存在血管疾病的情况下，内皮刺激-反应关系是否发生改变；2)确定在高脂血症患者服用HMG-Co a还原酶抑制剂6周后，内皮功能的变化是否对这种关系敏感。3)确定不同维管层的应力分布关系或周向应力分布是否不同。研究人员预计，这项研究将提高区分正常和受损内皮功能的能力，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MRI、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成为一名独立临床研究者的长期目标的理想选择，将创新的工程技术应用于面向患者的心血管问题。

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.