IVUS Detection of Rupture Prone Plaques

IVUS 检测易破裂斑块

• 批准号: 7373089
• 负责人: Marvin M Doyley
• 金额: $ 41.78万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7373089
• 关键词: Acoustics; American; Animal Model; Aorta; Arginine; Arterial Fatty Streak; Asparagine; Balloon Angioplasty; Behavior; Binding; Biological; Blood Vessels; Boston; Cardiovascular Diseases; Catheters; Cell Culture Techniques; Cells; Cessation of life; Clinical; Collaborations; Contrast Media; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary heart disease; DC101 Monoclonal Antibody; Data; Detection; Development; Diagnosis; Disease; Elements; Endothelium; Evaluation; Familial Hypercholesterolemia; Glycine; Goals; Gold; Human; Image; Imaging Device; Imaging Techniques; Inflammatory; Inflammatory Infiltrate; Leukocytes; Life; Lipids; Measures; Methods; Microbubbles; Modeling; Motion; Oryctolagus cuniculus; Patients; Peptides; Performance; Pharmacological Treatment; Plasma; Relative (related person); Research; Resolution; Rupture; Screening procedure; Sensitivity and Specificity; Severities; Site; Staging; Stress; Surface; Surface Antigens; System; Testing; Tissues; Ultrasonics; Ultrasonography; Vascular Endothelial Growth Factor Receptor; Weight; alanine aminopeptidase; arterial remodeling; base; density; design; flexibility; imaging modality; macrophage; mechanical behavior; migration; neovascular; neovasculature; novel; prevent; prototype; research study; second harmonic; vasa vasorum

DESCRIPTION (provided by applicant): Cardiovascular disease is the number one killer of Americans, claiming over 500,000 lives annually. These deaths occur when the fibrous cap of an atherosclerotic plaque ruptures in the later stages of the disease. Current screening tests for the diagnosis of coronary atherosclerosis is limited. Coronary angiography, the "gold standard" employed to assess the severity of coronary disease in symptomatic patients, reveals only the degree of luminal narrowing, and fails to visualize the arterial wall. Additionally, arterial remodeling prevents many plaques from being detected by coronary angiography. The overall goal of this proposal is to develop two pragmatic ultrasound-imaging techniques (neovascular imaging, and elastography imaging) to identify life threatening atherosclerotic plaques. The microvascular networks or vasa vasorum of developing atherosclerotic plaques may function as a conduit for the migration of leukocytes and plasma components into the arterial wall or into the endothelium on the arterial surface. These inflammatory cells, if allowed to accumulate, will weaken the fibrous cap. The resolution of intravascular ultrasound (IVUS) is not sufficiently high to visualize plaque neovasculature; therefore, we propose to develop a microbubble ultrasound contrast that binds preferentially to newly formed blood vessels. More specifically, we propose to conjugate a microbubble contrast agent to a peptide with the NGR-homing sequence that binds to CD13, and a monoclonal antibody, DC101, that binds to the VEGF receptor-2. The conjugated microbubbles will be visualized by employing the second harmonic contrast imaging mode, which we propose to implement on a commercial ultrasound IVUS scanner. The mechanical behavior of stable plaques is noticeably different from those of stable plaques. Circumferential stress will accumulate at the junction between the normal intima, and the fibrous cap overlaying the lipid pool in unstable plaques; whereas this does not occur in stable plaques. To differentiate between stable and unstable plaques based on their mechanical behavior we propose to visualize the stress distribution within vascular tissue using a novel prototype system for intravascular ultrasonic elastographic imaging. An atherosclerotic animal model will be employed to assess a) the sensitivity and specificity of detecting life-threatening plaques with both imaging approaches as standalone methods will be assessed relative to a combined microvascular-elastography imaging approach, and b) the feasibility of predicting the propensity of plaque to rupture based on the three imaging approaches. A successful out come of the proposed may prove to be beneficial to the over 50 million Americans who are unaware that they may be suffering from advance coronary atherosclerosis and should be placed on a lipid-lowering dietary and pharmacological treatment.

描述（由申请人提供）：心血管疾病是美国人的第一杀手，每年夺去超过500,000人的生命。当疾病后期的动脉粥样硬化斑块破裂时，这些死亡发生。当前诊断冠状动脉粥样硬化的筛查测试受到限制。冠状动脉造影是评估有症状患者冠状动脉疾病严重程度的“黄金标准”，仅显示腔狭窄的程度，并且无法可视化动脉壁。此外，动脉重塑可防止许多斑块被冠状动脉造影检测到。该提案的总体目标是开发两种务实的超声检查技术（新血管成像和弹性成像），以识别威胁性动脉粥样硬化斑块。开发动脉粥样硬化斑块的微血管网络或VASA血管可以充当白细胞和血浆成分迁移到动脉壁或动脉表面的内皮中的管道。这些炎症细胞（如果允许积累）将削弱纤维帽。血管内超声（IVU）的分辨率不足以可视化斑块新生血管系统。因此，我们建议开发一种微泡超声对比，该对比优先与新形成的血管结合。更具体地说，我们建议将微气泡的对比剂与肽与结合CD13结合的NGR-HOMING序列以及与VEGF受体-2结合的单克隆抗体DC101。共轭微泡将通过采用第二种谐波对比成像模式来可视化，我们建议在商业超声IVUS扫描仪上实施。稳定斑块的机械行为与稳定斑块的机械行为明显不同。圆周应力将在正常内膜之间的连接处积累，而纤维帽将脂质池叠加在不稳定的斑块中。而这不会在稳定的斑块中发生。为了根据其机械行为来区分稳定的斑块和不稳定的斑块，我们建议使用新型的原型系统用于可视化血管组织内的应力分布，用于血管内超声弹性成像。将采用动脉粥样硬化动物模型来评估a）通过两种成像方法检测威胁生命的斑块的敏感性和特异性，将对独立方法进行评估，相对于一种基于三种成像方法，预测plaque to Reputture的可行性的可行性，将评估相对于合并的微血管塑造成像方法的敏感性和特异性。提议的成功来源可能被证明对超过5000万美国人有益，他们不知道自己可能患有预先冠状动脉粥样硬化，应将其放置在降低脂质的饮食和药理治疗中。