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: 8166176
• 负责人: John A Allen
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166176
• 关键词: Acoustics; Acute; Area; Arterial Fatty Streak; Atherosclerosis; Binding; Biological Markers; Blood flow; Cardiovascular Diseases; Classification; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Coronary; Coronary Angiography; Death Rate; Encapsulated; Filipino; Frequencies; Funding; General Population; Grant; Hawaii; Hawaiian population; Health Care Costs; Heart Diseases; Hospitalization; Image; Inflammation; Institution; Leukocytes; Ligands; Lipids; Microbubbles; Morbidity - disease rate; Myocardial Infarction; Nutrient; Patients; Physiological; Recommendation; Research; Research Personnel; Resources; Risk; Rupture; Shadowing (Histology); Signal Transduction; Site; Source; Staging; Stimulus; System; Ultrasonography; United States; United States National Institutes of Health; Vascular remodeling; diet and exercise; high risk; imaging modality; molecular imaging; mortality; neovascularization; prevent; response; shear stress; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. We are investigating the targeting efficacy in physiological flow conditions for large vessels and the optimal acoustical response of targeted agents at high frequency.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 心血管疾病是夏威夷和美国发病率和死亡率的主要原因。在对夏威夷的心血管疾病死亡率进行更仔细的研究后，菲律宾人和夏威夷土著人的死亡率明显高于一般人口。此外，心血管疾病占住院国家医疗保健费用的很大一部分。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对应的斑块破裂相关。 饮食和运动方面的建议已被开发，以防止动脉粥样硬化性心血管疾病，但较少的努力，以帮助患者谁可能是脆弱的斑块破裂的风险。 冠状动脉造影术具有局限性，因为它不允许检查血管壁，只能确定血管腔的狭窄。血管内超声（IVUS）提供了动脉壁的二维横截面视图，并提供了确定管腔和血管面积的能力。然而，斑块分类存在严重局限性。高频信号可能与声学阴影方面混淆。斑块破裂的机制还没有很好的理解，目前还没有成像模式，可以鲁棒地检测易损斑块。 易损斑块的特征是一个大的脂质核心与薄和发炎的纤维帽。来自周围血流的低内皮剪切应力可作为早期纤维粥样硬化进展和分化为高危斑块的刺激。假设血管外膜的营养来源是血管小血管，它可以作为白色血细胞迁移到血管壁内层的通道。随后，在这些斑块内可发生扩张性血管重塑。血管内超声探针的分子成像能力的增加将为检测斑块破裂的生物标志物（如新生血管和炎症）提供改进。靶向超声造影剂是带有配体的微泡，使其能够结合到特定的病变部位。IVUS探头的中心频率（35-50 MHz）远高于常规诊断超声系统。我们正在研究大血管生理流动条件下的靶向功效以及靶向药物在高频下的最佳声学响应。