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: 7959175
• 负责人: John A Allen
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959175
• 关键词: Acoustics; Acute; Area; Arterial Fatty Streak; Binding; Biological Markers; Blood flow; Cardiovascular Diseases; Cessation of life; Classification; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Coronary; Coronary Angiography; Disease; Encapsulated; Filipino; Frequencies; Funding; General Population; Grant; Hawaii; Hawaiian population; Health Care Costs; Heart; Hospitalization; Image; Inflammation; Institution; Leukocytes; Ligands; Lipids; Medical; Microbubbles; Nutrient; Outcomes Research; 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 illness and death in the United States and in Hawaii. Upon closer examination of the mortality rate from cardiovascular disease in Hawaii, it is clear that Filipinos and Native Hawaiians have a disproportionally higher mortality rate than the general population. Moreover, cardiovascular disease is a responsible for a significant portion of the state health care costs from hospitalizations. Sudden cardiac death and acute heart often occur without warning and these complications are typically associated with a plaque rupture corresponding to advanced stages of coronary atherosclerotic disease. Recommendations in terms in diet and exercise have been developed to prevent the onset of atherosclerotic disease but less effort has been made to aid patients who may be at risk for vulnerable plaque rupture. Coronary angiography has limitations as it does not allow for inspection of the vessel wall and can only determine narrowing of the luminal. Intravascular ultrasound (IVUS) provides a two dimensional cross sections view of the arterial wall and offers some ability to determine lumen and vessels areas. However, severe limitations exist in the classifications of plaques. The high frequency signal may be confused with acoustic shadowing aspects. The mechanisms of plaque rupture are not well understood and currently 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 vasa vasorum which supplies nutrients to the adventia may serve as a means for which white blood cells migrate into the lining of the 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 which 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 investigate 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。 在美国和夏威夷，心血管疾病是疾病和死亡的主要原因。仔细检查夏威夷心血管疾病的死亡率后，可以明显看出，菲律宾人和夏威夷原住民的死亡率比一般人群高得多。此外，心血管疾病是一个负责从住院的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疾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疾病的发作，但较少的努力已经作出了帮助患者谁可能是危险的易损斑块破裂。 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，严重的局限性存在于斑块的分类。 高频信号可能会与声学阴影方面混淆。 斑块破裂的机制还没有很好地理解，目前没有成像模式，目前存在的，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风险斑块的刺激。 有人假设，为外膜提供营养的血管可能是白色血细胞迁移到壁内层的一种方式。 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提供在检测斑块破裂的生物标志物方面的改进，例如新血管形成和炎症。 靶向超声造影剂是具有附着配体的封装微泡，所述配体允许它们结合到特定的患病部位。 IVUS探头的中心频率（35-50 MHz）远高于常规诊断超声系统。 我们研究了大血管在生理流动条件下的靶向效果和靶向药物在高频下的最佳声学响应。