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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在美国和夏威夷，心血管疾病是导致疾病和死亡的主要原因。仔细研究夏威夷的心血管疾病死亡率，很明显，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。心脏性猝死和急性心脏病经常在没有征兆的情况下发生，这些并发症通常与晚期冠状动脉粥样硬化性疾病的斑块破裂有关。在饮食和锻炼方面的建议已经被制定出来，以防止动脉粥样硬化性疾病的发病，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。斑块破裂的机制目前还不清楚，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。据推测，为先天痴呆提供营养的血管可能是白细胞迁移到壁层的一种手段。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。我们研究了大血管在生理流动条件下的靶向效能，以及靶向制剂在高频下的最佳声学响应。

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.