Comprehensive Magnetic Resonance in PAD

描述(申请人提供)：外周动脉疾病(PAD)的特征是动脉粥样硬化导致的下肢动脉阻塞。在美国超过1000万的PAD患者中，大多数是老年人，而且患病率还在不断上升。与冠心病患者相比，PAD患者接受了潜在的挽救生命的危险因素修改。目前使用的诊断方法有限，显然需要能够研究疾病进展和消退的方法。因此，已经组建了一个来自心脏病学、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来开发和完善这些方法。目的#1开发和测试磁共振成像(MRI)方法以成像动脉壁并表征PAD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，以快速检测股浅动脉的血管壁和动脉粥样硬化斑块。多光谱磁共振成像将表征特定区域的斑块成分。目的#2开发和测试MRI和MR波谱方法，以定量动脉粥样硬化周围动脉供应的骨骼肌的血流和能量。在MRI中将进行标准化的屈膝运动，以达到特定的功率输出。运动高峰时首次通过对比剂增强MRI将量化小腿肌肉低灌注的严重程度。31在运动恢复过程中获得的磷光谱将确定缺血的代谢证据。磁共振血管造影术将评估管腔阻塞。机能研究将包括6分钟步行试验和跑步机运动，测量V02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指标，目标3是使用多模式磁共振来测试他汀类药物对PAD中血管壁、动脉粥样硬化斑块、骨骼肌灌注和能量的疗效。100名踝臂指数在0.4到0.9之间的PAD患者将在使用大剂量他汀类药物治疗的4年中，在基线和每年进行全面的MR检查。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终末器官功能的了解，并为其他新疗法的研究奠定基础。

DESCRIPTION (provided by applicant): 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 under treated 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. Therefore, 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. 31Phosphorus 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. 100 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.