IVUS Detection of Rupture Prone Plaques

描述（由申请人提供）：心血管疾病是美国人的头号杀手，每年夺去50多万人的生命。这些死亡发生在动脉粥样硬化斑块的纤维帽在疾病的后期破裂时。目前用于诊断冠状动脉粥样硬化的筛查试验是有限的。冠状动脉血管造影术是用于评估有症状患者冠状动脉疾病严重程度的“金标准”，它只能显示管腔狭窄的程度，而不能显示动脉壁。此外，动脉重塑阻止了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实用的超声成像技术（新生血管成像和弹性成像），以识别危及生命的动脉粥样硬化斑块。发展中的动脉粥样硬化斑块的微血管网络或血管可以作为白细胞和血浆组分迁移到动脉壁或动脉表面上的内皮中的管道。这些炎性细胞，如果允许积累，将削弱纤维帽。血管内超声（IVUS）的分辨率不足以显示斑块新生血管;因此，我们建议开发一种优先结合新形成血管的微泡超声造影剂。更具体地说，我们提出将微泡造影剂与具有结合CD 13的NGR归巢序列的肽和结合VEGF受体-2的单克隆抗体DC 101缀合。共轭微泡将采用二次谐波造影成像模式，我们建议实现商业超声IVUS扫描仪可视化。稳定斑块的力学行为与稳定斑块的力学行为明显不同。在不稳定斑块中，周向应力将在正常内膜和覆盖脂质池的纤维帽之间的交界处累积;而在稳定斑块中不会发生这种情况。为了区分稳定和不稳定的斑块的基础上，他们的机械行为，我们建议可视化血管组织内的应力分布使用一种新的原型系统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）使用两种成像方法检测危及生命的斑块的灵敏度和特异性，因为将相对于组合的微血管弹性成像方法评估独立方法，和B）基于三种成像方法预测斑块破裂倾向的可行性。一个成功的建议可能会被证明是有益的，超过5000万美国人谁不知道他们可能患有冠状动脉粥样硬化，并应放置在降脂饮食和药物治疗。

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.