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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 心血管疾病是夏威夷和美国发病率和死亡率的主要原因。根据对夏威夷心血管疾病死亡率的仔细研究，菲律宾人和夏威夷原住民的死亡率比一般人高得不成比例。此外，心血管疾病占国家医疗保健住院费用的很大一部分。心源性猝死和急性心脏病发作经常在没有征兆的情况下发生，这些并发症通常与冠状动脉粥样硬化性心脏病晚期斑块破裂有关。在饮食和运动方面的建议已经被制定出来，以预防动脉粥样硬化性心血管疾病，但对可能有脆弱斑块破裂风险的患者的帮助努力较少。冠状动脉造影术有局限性，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断面图，并提供了一些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遮挡方面混淆。斑块破裂的机制还不是很清楚，目前还没有一种成像手段可以很好地检测到脆弱的斑块。 易损斑块的特征是有一个大的脂核和一个薄而发炎的纤维帽。来自周围血流的低内皮剪切力可作为早期纤维动脉粥样硬化进展和分化为高危斑块的刺激因素。据推测，为血管血管提供营养物质的血管可能是白细胞迁移到血管壁衬里的管道。随后，扩张性血管重塑可在这些斑块内发生。IVUS探头的分子成像能力的增加将在检测斑块破裂的生物标记物方面提供改进，如新生血管和炎症。靶向超声造影剂是带有附加配体的微泡，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)远高于常规超声诊断仪。在前一年中，我们使用了从患者身上切除的冠状动脉。现在，这项工作已经扩展到小鼠斑块的动物模型。

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.