Integrated MRI-Based Examination for Evaluation of Peripheral Arterial Disease

用于评估外周动脉疾病的基于 MRI 的综合检查

• 批准号: 7933881
• 负责人: Felix W Wehrli
• 金额: $ 44.86万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933881
• 关键词: Accounting; Address; Affect; Age; American; Angiography; Ankle; Arterial Fatty Streak; Arteries; Atherosclerosis; Blood; Blood Vessels; Blood flow; Cardiovascular system; Carotid Arteries; Clinical; Competence; Cost Control; Data; Descending aorta; Development; Diagnosis; Disease; Disease Association; Ensure; Evaluation; Event; Future; General Population; Health Care Costs; Heart; Human Resources; Image; Intermittent Claudication; Intervention; Label; Length; Life Style; Location; Lower Extremity; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Meta-Analysis; Methodology; Methods; Metric; Modality; Monitor; Myocardial Infarction; Nature; Obstruction; Onset of illness; Outcomes Research; Oxygen; Patients; Peripheral Vascular Diseases; Peripheral arterial disease; Persons; Pharmaceutical Preparations; Physicians' Offices; Physiologic pulse; Physiological; Population; Preventive; Procedures; Protocols documentation; Research Personnel; Risk Factors; Roentgen Rays; Screening procedure; Site; Specificity; Speed; Staging; Stenosis; Stimulus; Stroke; Structure of popliteal artery; Symptoms; System; Systolic Pressure; Techniques; Testing; Thick; Time; Travel; Ultrasonography; Veins; Venous; Work; X-Ray Computed Tomography; age related; base; brachial artery; cardiovascular risk factor; femoral artery; high risk; indexing; insight; noninvasive diagnosis; peer; pre-clinical; prognostic; public health relevance; reactive hyperemia; tonometry; tool

DESCRIPTION (provided by applicant): Peripheral arterial disease (PAD) affects about 8 million Americans. The disease is typically caused by atherosclerosis and thus is systemic in nature. PAD's clinical manifestations are caused by stenosing of the major arteries supplying the lower extremities (iliac, femoral and popliteal arteries). The condition has further been recognized as an independent risk factor for future cardiovascular events, in particular myocardial infarction and stroke. The initial test for diagnosing PAD is measurement of the ankle-brachial index (ABI), a simple inexpensive test typically performed in a physician's office. However, while being highly specific, the test's sensitivity is low. Thus, while low ABI is a strong indicator of elevated cardiovascular risk, a normal ABI does not rule out high risk due to the test's high false negative rate. The ABI is therefore of limited utility as a screening tool for the general population. It is well known that more subtle functional deficits precede the build-up of atherosclerotic lesions (which at a later stage cause obstructions or vulnerable plaques that can trigger a vascular event). It would therefore be particularly beneficial, both to the patient and also from a healthcare cost containment point of view, if the onset of the disease could be determined well before it becomes symptomatic, so as to allow for lifestyle changes or preventive drug intervention. Among the early manifestations of PAD is decreased vascular compliance and impaired microvascular reactivity, which has been suggested to provide better prognostic assessment in the general population. Microvascular reactivity is typically evaluated on the basis of a measurement of reactive hyperemic indices by ultrasound, performed in the brachial artery, which, however, is not a common site of PAD. Compliance is often inferred from a measurement of pulse wave velocity (PWV), which is proportional to vessel wall stiffness, and thus is inversely related to compliance. PWV is usually quantified from the time lag of the systolic pressure wave between a location in the carotid artery and a point in the femoral artery using tonometry, an approach that is problematic since the path length the blood travels can only be estimated. Thus, the current approaches have limitations and there is no single modality that allows noninvasive quantification of the various physiological parameters that may predispose a subject to develop PAD and, by association, augment a person's cardiovascular risk in general. We have, in preliminary work in support of this proposal, conceived and reduced to practice, new MRI- based techniques for measuring multiple parameters as part of a single examination, including (1) a measurement of microvascular reactivity based on monitoring the temporal changes in venous oxygen saturation serving as an endogenous label in the femoral artery and vein during reactive hyperemia, (2) a high- speed, ungated, projection-based technique for measuring time-resolved arterial blood flow, (3) a method for deriving aortic pulse-wave velocity and compliance (which accounts for 60-70% of systemic arterial compliance), by combining #2 with an image-based measurement of aortic path length. We hypothesize that the measured parameters vary characteristically with age and degree of peripheral vascular disease. We will evaluate the above hypotheses by addressing the following specific aims: 1. Fully implement, and evaluate, a high-speed projection technique for measurement of time-resolved aortic blood flow in a single heart beat simultaneously in the ascending and descending aorta for quantifying pulse-wave velocity and compliance. 2. Integrate the method of aim #1 with the previously developed oximetric technique for quantifying microvascular reactivity into a single protocol. 3. Apply the protocol of aim #2 to subjects, ages 25-65 years, without significant cardiovascular risk factors, characterized further by ABIe0.9, and subjects in the age range of 46-65 years who have PAD based on ABI<0.9 to address the question whether in healthy subjects (i) the metrics derived with the protocol of aim #2 vary in an age-dependent manner including the hypothesized decrease in overall systemic compliance and decreased microvascular reactivity; (ii) subjects with PAD, age-matched to healthy controls, have lower systemic compliance and microvascular reactivity than their healthy peers. Public Health Relevance: The expected outcome of this research is that the results will provide new insight into the early manifestations of PAD and the age-related changes in micro- and macrovascular competence of the arterial system through an entirely noninvasive procedure. Since the methodology to be used in the proposed project is largely in place the investigators have confidence that the project can be completed within the allotted time frame. Lastly, the project ensures retention of personnel in compliance with the stimulus initiative. There is currently no sensitive noninvasive for diagnosing preclinical peripheral arterial disease (PAD), which affects 8 million Americans. In this project we propose to implement and evaluate a new noninvasive MRI-based method in healthy subjects and patients with PAD to address the hypothesis that the measured parameters vary characteristically with age and degree of peripheral vascular disease.

描述（由申请人提供）： 外围动脉疾病（PAD）影响约800万美国人。该疾病通常是由动脉粥样硬化引起的，因此本质上是全身性的。 PAD的临床表现是由供应下肢的主要动脉st狭窄引起的。该病情进一步被认为是未来心血管事件的独立危险因素，特别是心肌梗塞和中风。诊断垫的初步测试是测量脚踝 - 桥梁指数（ABI），这是一种简单的廉价测试，通常在医生的办公室中进行。但是，尽管高度具体，但测试的灵敏度却很低。因此，尽管低ABI是心血管风险升高的有力指标，但由于测试的高假阴性率，正常ABI并不排除高风险。因此，ABI作为一般人群的筛选工具的实用性有限。众所周知，在动脉粥样硬化病变的堆积之前，功能缺陷更为细微（在以后会导致障碍物或易受伤害的斑块，可能触发血管事件）。因此，如果在疾病的开始之前可以确定疾病的发作，那么这对患者以及从医疗保健成本遏制的角度来说都是特别有益的，以便允许生活方式改变或预防药物干预。 PAD的早期表现包括降低血管依从性和微血管反应性受损，这已建议在普通人群中提供更好的预后评估。通常根据在臂动脉中进行的超声测量反应性高血压指数评估微血管反应性，然而，这并不是PAD的常见部位。通常是根据对脉搏波速度（PWV）的测量来推断的，该脉冲波速度与容器壁刚度成正比，因此与依从性成反比。通常从颈动脉中的位置与股动脉中的位置之间的收缩压波的时间滞后来定量PWV，这是一种有问题的方法，这是一种有问题的方法，因为只能估计血液流动的路径长度。因此，当前的方法有局限性，没有单一的方式可以无创量化各种生理参数，这些参数可能会使受试者易于发展PAD，并且通过关联，可以增强一个人的心血管风险。在支持该提案的初步工作中，我们已经构思和简化为实践，新的基于MRI-基于多个参数的技术，作为单个检查的一部分，包括（1）基于监测静脉氧饱和度的时间变化的微血管反应性的测量，将其作为静脉氧饱和度的静脉饱和度变化，作为在股骨中的内源性耐药性，并在股骨中均具有速度，并且在股骨中的速度较高，并且在反应型（2），并且在Reative of Reative of Reative of Reative of Reative of Reative，（2测量时间分辨的动脉血流的技术，（3）一种推导主动脉脉冲波速度和依从性的方法（占全身动脉依从性的60-70％），通过将＃2与基于图像的主动脉式路径长度相结合。我们假设测得的参数随着年龄和外周血管疾病的程度而变化。我们将通过解决以下特定目的来评估上述假设：1。完全实施和评估，这是一种高速投影技术，用于测量单个心脏跳动中时间分辨的主动脉血流，同时在上升和下降主动脉中，以量化脉冲波速度和合规性。 2。将目标＃1的方法与先前开发的Oximetric技术整合在一起，以将微血管反应性量化为单个方案。 3。将目标＃2的协议应用于25-65岁的受试者，没有明显的心血管危险因素，进一步以ABIE0.9的特征，以及46-65岁的年龄范围内的受试者在46-65岁的年龄范围内基于ABI <0.9的PAD <0.9，以解决健康主题中的问题（i）在包括年龄符合年龄范围的范围内的整体范围中，该问题是否符合量子＃2 vare的范围，包括年龄prodepriendation nepsiand of Aim poss part of Aim＃2 vare的协议。微血管反应性； （ii）与健康同龄人相比，与健康对照相匹配的垫子，与健康对照相匹配的受试者具有较低的全身性依从性和微血管反应性。 公共卫生相关性： 这项研究的预期结果是，结果将为PAD的早期表现以及与年龄相关的动脉系统微血管能力的变化提供新的见解，这是通过完全无创的程序来提供的。由于在拟议的项目中使用的方法在很大程度上是适当的，因此调查人员有信心可以在分配的时间范围内完成该项目。最后，该项目确保了遵守刺激倡议的人员保留人员。目前尚无对诊断临床前动脉疾病（PAD）（影响800万美国人的临床前动脉疾病（PAD）的敏感无创。在该项目中，我们建议在健康受试者和PAD患者中实施和评估一种新的非侵入性MRI方法，以解决以下假设：测量参数随着年龄和外围性血管疾病程度的特征而变化。