IVUS Detection of Rupture Prone Plaques

IVUS 检测易破裂斑块

• 批准号: 8490409
• 负责人: Marvin M Doyley
• 金额: $ 35.02万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490409
• 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; Diet; Disease; Elements; Endothelium; Evaluation; Familial Hypercholesterolemia; Glycine; Goals; Gold; Homing; 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; 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; elastography; flexibility; imaging modality; macrophage; mechanical behavior; migration; neovascular; neovasculature; novel; prevent; prototype; research study; screening; 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(申请人提供)：心血管疾病是美国人的头号杀手，每年夺走超过50万人的生命。当动脉粥样硬化斑块的纤维帽在疾病后期破裂时，这些死亡就会发生。目前诊断冠状动脉粥样硬化的筛查试验是有限的。冠状动脉造影术是用来评估有症状患者冠状动脉病变严重程度的“金标准”，它只显示管腔狭窄的程度，而不能显示动脉壁。此外，动脉重塑可防止冠状动脉造影术发现许多斑块。这项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)来识别威胁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能起到将白细胞和血浆成分迁移到动脉壁或动脉表面的内皮细胞中的管道的作用。这些炎症细胞，如果任其积聚，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，我们建议开发一种微泡超声造影剂，优先结合新形成的血管。更具体地说，我们建议将微泡造影剂与与CD13结合的NGR归巢序列的多肽以及与VEGF受体-2结合的单抗DC101偶联。共轭微泡将通过采用二次谐波对比成像模式来可视化，我们建议在商用超声IVUS扫描仪上实现该模式。稳定斑块的力学行为明显不同于稳定斑块。在不稳定斑块中，正常内膜和覆盖在脂质池上的纤维帽之间的交界处会积累周向应力；而在稳定斑块中则不会发生这种情况。为了根据斑块的力学行为来区分稳定斑块和不稳定斑块，我们建议使用一种新的血管内超声弹性成像原型系统来可视化血管组织内的应力分布。动脉粥样硬化动物模型将被用来评估a)作为独立方法的两种成像方法检测危及生命的斑块的敏感性和特异性将相对于微血管-弹性成像成像方法进行评估，以及b)基于三种成像方法预测斑块破裂倾向的可行性。拟议中的成功结果可能会证明对5000多万美国人有利，他们没有意识到自己可能患有晚期冠状动脉粥样硬化，应该接受降脂饮食和药物治疗。

项目成果

Noninvasive vascular displacement estimation for relative elastic modulus reconstruction in transversal imaging planes.

• DOI: 10.3390/s130303341
• 发表时间: 2013-03-11
• 期刊: Sensors (Basel, Switzerland)
• 作者: Hansen HH;Richards MS;Doyley MM;de Korte CL
• 通讯作者: de Korte CL

Investigating the impact of spatial priors on the performance of model-based IVUS elastography.

• DOI: 10.1088/0031-9155/56/22/014
• 发表时间: 2011-11-21
• 期刊: Physics in medicine and biology
• 影响因子: 3.5
• 作者: Richards MS;Doyley MM
• 通讯作者: Doyley MM

Elastography: general principles and clincial applications.

• DOI: 10.1016/j.cult.2013.09.006
• 发表时间: 2014-01
• 期刊: Ultrasound clinics

The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid-shelled microbubble contrast agent.

• DOI: 10.1016/j.ultrasmedbio.2014.01.002
• 发表时间: 2014-04
• 期刊: ULTRASOUND IN MEDICINE AND BIOLOGY
• 影响因子: 2.9
• 作者: Shekhar, Himanshu;Awuor, Ivy;Thomas, Keri;Rychak, Joshua J.;Doyley, Marvin M.
• 通讯作者: Doyley, Marvin M.

Parametric subharmonic imaging using a commercial intravascular ultrasound scanner: an in vivo feasibility study.

• DOI: 10.7863/jum.2012.31.3.361
• 发表时间: 2012-03
• 期刊: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
• 作者: Eisenbrey JR;Sridharan A;deMuinck ED;Doyley MM;Forsberg F
• 通讯作者: Forsberg F