ACT 1 PROJ 2 TARGETED HIGH-FREQUENCY ULTRASOUND-CONTRAST AGENT IMAGING

行动 1 项目 2 定向高频超声造影剂成像

• 批准号: 8357170
• 负责人: John A Allen
• 金额: $ 16.18万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357170
• 关键词: Acoustics; Acute; Animal Model; Area; Arterial Fatty Streak; Atherosclerosis; Binding; Biological Markers; Blood flow; Cardiovascular Diseases; Classification; Contrast Media; Coronary; Coronary Angiography; Coronary artery; Death Rate; Encapsulated; Filipino; Frequencies; Funding; General Population; Grant; Hawaii; Hawaiian population; Health Care Costs; Heart Diseases; Hospitalization; Image; Inflammation; Leukocytes; Ligands; Lipids; Microbubbles; Morbidity - disease rate; Mus; Myocardial Infarction; National Center for Research Resources; Nutrient; Patients; Principal Investigator; Recommendation; Research; Research Infrastructure; Resources; Risk; Rupture; Shadowing (Histology); Signal Transduction; Site; Source; Staging; Stimulus; System; Ultrasonography; United States; United States National Institutes of Health; Vascular remodeling; Work; cost; diet and exercise; high risk; imaging modality; infrastructure development; molecular imaging; mortality; neovascularization; prevent; shear stress; success; sudden cardiac death; two-dimensional; vasa vasorum

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cardiovascular disease is a leading cause of morbidity and mortality in Hawaii and the United States. Upon closer examination of cardiovascular disease death rates in Hawaii, Filipinos and Native Hawaiians have disproportionally higher mortality rates than the general population. Moreover, cardiovascular disease is responsible for a significant portion of the state health care costs from hospitalizations. Sudden cardiac death and acute heart attack often occur without warning and these complications are typically associated with a plaque rupture corresponding to advanced stages of coronary atherosclerotic heart disease. Recommendations in terms of diet and exercise have been developed to prevent atherosclerotic cardiovascular disease, but less effort has been made to aid patients who may be at risk for vulnerable plaque rupture. Coronary angiography has limitations because it does not allow for inspection of the vessel wall and can only determine narrowing of the vessel lumen. Intravascular ultrasound (IVUS) provides a two-dimensional cross-sectional view of the arterial wall and offers some ability to determine lumen and vessel areas. However, severe limitations exist in the classification of plaques. The high frequency signal may be confused with acoustic shadowing aspects. The mechanisms of plaque rupture are not well understood and no imaging modality currently exists which can robustly detect vulnerable plaques. Vulnerable plaques are characterized by a large lipid core with a thin and inflamed fibrous cap. Low endothelial shear stress from the surrounding blood flow can serve as stimulus for the progression and differentiation of an early fibroatheroma to a high-risk plaque. It has been hypothesized that the vasa vasorum, which supplies nutrients to the adventia, may serve as a conduit for white blood cells to migrate into the lining of the vessel wall. Subsequently, expansive vascular remodeling can occur within these plaques. The addition of molecular-imaging capabilities to IVUS probes would provide an improvement in detecting biomarkers for plaque rupture, such as neovascularization and inflammation. Targeted ultrasound contrast agents are encapsulated microbubbles with attached ligands that allow them to bind to specific diseased sites. The center frequency of IVUS probes (35-50 MHz) is much higher than conventional diagnostic ultrasound systems. During the previous year we utilized excised coronary arteries from patients. Now the work has been extended to an animal model of plaque in mice.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 心血管疾病是夏威夷和美国发病和死亡的主要原因。经过对夏威夷心血管疾病死亡率的仔细检查，菲律宾人和夏威夷原住民的死亡率比一般人群高得不成比例。此外，心血管疾病占州住院医疗费用的很大一部分。心源性猝死和急性心脏病发作经常在没有警告的情况下发生，这些并发症通常与冠状动脉粥样硬化性心脏病晚期的斑块破裂有关。 已经制定了饮食和运动方面的建议来预防动脉粥样硬化性心血管疾病，但为帮助可能面临易损斑块破裂风险的患者所做的努力较少。冠状动脉造影有局限性，因为它不能检查血管壁，只能确定血管管腔的狭窄程度。血管内超声 (IVUS) 提供动脉壁的二维横截面视图，并提供一定程度的确定管腔和血管面积的能力。然而，斑块的分类存在严重的局限性。高频信号可能与声学阴影方面相混淆。斑块破裂的机制尚不清楚，目前不存在可以稳健检测易损斑块的成像方式。 易损斑块的特征是具有大的脂质核心和薄且发炎的纤维帽。来自周围血流的低内皮剪切应力可以刺激早期纤维粥样斑块进展和分化为高风险斑块。据推测，为外膜提供营养的血管滋养管可能充当白细胞迁移到血管壁内壁的管道。随后，这些斑块内可能发生扩张性血管重塑。 IVUS 探针增加分子成像功能将改善斑块破裂生物标志物（例如新血管形成和炎症）的检测。靶向超声造影剂是带有配体的封装微泡，使它们能够结合到特定的病变部位。 IVUS 探头的中心频率 (35-50 MHz) 远高于传统诊断超声系统。去年，我们使用了从患者身上切除的冠状动脉。现在，这项工作已扩展到小鼠斑块动物模型。