COMPREHENSIVE MAGNETIC RESONANCE IN PERIPHERAL ARTERIAL DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 外周动脉疾病（PAD）的特征是由于动脉粥样硬化引起的下肢动脉阻塞。在美国超过1000万的PAD患者中，大多数是老年人，患病率正在增加。与冠状动脉疾病患者相比，PAD患者在潜在挽救生命的风险因素调整方面治疗不足。目前使用的诊断方法是有限的，明确需要允许研究疾病进展和消退的模式。一个来自心脏病学、放射学、血管外科、生物医学工程、运动科学、生物统计学和临床试验管理的多学科团队已经组建起来，以开发和完善这些方法。目的#1是开发和测试磁共振成像（MRI）方法，以成像动脉壁并表征PAD中的动脉粥样硬化斑块。将在正常受试者中开发高分辨率多层黑血螺旋MRI，并在患者中进行测试，以快速调查股浅动脉中的血管壁和动脉粥样硬化斑块。多光谱MRI将表征特定区域的斑块成分。目的#2是开发和测试MRI和MR光谱方法，用于量化由动脉粥样硬化外周动脉供应的骨骼肌的灌注和能量学。 将在MRI中进行标准化跖屈运动至特定功率输出。在运动高峰期进行首过对比增强MRI将量化小腿肌肉灌注不足的严重程度。在运动恢复期间获得的磷光谱将识别缺血的代谢证据。MR血管造影将评估管腔阻塞。功能研究将包括6分钟步行试验和跑步机运动，测量VO 2峰值。假设他汀类药物治疗将减少斑块负荷，稳定斑块成分，并改善终末器官功能的测量。目的#3是使用多模态磁共振检测他汀类药物治疗对血管壁、动脉粥样硬化斑块以及PAD中骨骼肌灌注和能量学的疗效。90例踝臂指数在0.4 - 0.9之间的PAD患者将在基线时和4年高剂量他汀类药物治疗期间每年进行全面MR研究。这些研究将加深对他汀类药物介导的斑块消退和稳定以及改善PAD终末器官功能的理解，并为其他新疗法的研究奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. Most of the over 10 million in the U.S. with PAD are elderly and the prevalence is increasing. Patients with PAD are undertreated with potentially life-saving risk factor modification when compared to those with coronary disease. Presently used diagnostic methods are limited and modalities that will allow study of progression and regression of disease are clearly needed. A multi-disciplinary team from cardiology, radiology, vascular surgery, biomedical engineering, exercise science, biostatistics and clinical trials management has been assembled to develop and refine such methods. Aim #1 is to develop and test magnetic resonance imaging (MRI) methods to image the arterial wall and characterize atherosclerotic plaque in PAD. High-resolution multislice black-blood spiral MRI will be developed in normal subjects and tested in patients to rapidly survey the vessel wall and atherosclerotic plaque in the superficial femoral artery. Multi-spectral MRI will characterize plaque components in specific regions. Aim #2 is to develop and test MRI and MR spectroscopic methods in the quantification of perfusion and energetics of skeletal muscle supplied by atherosclerotic peripheral arteries. Standardized plantarflexion exercise to a specific power output in the MRI will be performed. First-pass contrast-enhanced MRI at peak exercise will quantify the severity of calf muscle hypoperfusion. Phosphorus spectra acquired during exercise recovery will identify the metabolic evidence for ischemia. MR angiography will assess luminal obstruction. Functional studies will include 6-minute walk test and treadmill exercise with measures of V02 peak. With the hypothesis that statin therapy will reduce plaque burden, stabilize plaque components, and improve measures of end-organ function. Aim #3 is to use multi-modality magnetic resonance to test the efficacy of statin therapy on the vessel wall, atherosclerotic plaque, and skeletal muscle perfusion and energetics in PAD. 90 patients with PAD with an ankle-brachial index between 0.4 and 0.9 will be studied with comprehensive MR at baseline and yearly during 4 years of therapy with a high-dose statin. These studies will enhance the understanding of statin-mediated plaque regression and stabilization and improved end organ function in PAD and lay the groundwork for the study of other novel therapies.