TARGETED ULTRASOUND CONTRAST ASSISTED IMAGING OF BACTERIAL ENDOCARDITIS

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。 心内膜炎通常伴随着心脏瓣膜上生物膜的形成。心内膜炎的死亡率可达70%以上，因为治疗通常仅限于静脉注射抗菌药物或手术。可能需要长时间的抗生素治疗。此外，心内膜炎的瓣膜摘除和替换是一项困难和昂贵的程序。一种提供这种细菌生物膜的分子信息的非侵入性诊断方法将促进心内膜炎检测和治疗的重大改进。超声成像在可获得性、成本和便携性方面具有独特的优势，此外还提供与靶向超声造影剂联合使用的分子成像能力。这些试剂是被包裹的气体，当它们在声场中非线性振荡时，具有独特的散射特性，选择性地结合到特定的病变组织上，从而便于目标的检测和成像。我们试图为与心内膜炎相关的细菌生物膜开发一种有针对性的分子成像方法；然而，需要一些初步的探索性研究来推进这一超声造影剂辅助成像的新领域。我们试图在固定的环境流体中研究a)抗体靶向超声造影剂的生物膜附着，b)作为结合和声学参数的函数的声散射，以及c)细菌生存对声散射特征的影响。未来的临床成功取决于瓣膜结合的稳健性和受血流影响的声学散射信号。因此，我们还将研究与心脏瓣膜相似的生理相关情况和解剖结构(连续流动，不同的结合表面)的结合和声散射。

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. Endocarditis is often accompanied by the formation of a biofilm known as a vegetation on a cardiac valve. The mortality rate for endocarditis can be upward of 70% as the treatment is typically limited to intravenous antibotics or surgery. Prolonged antibiotic treatment may be required. Furthermore, valve removal and replacement for endocarditis is a difficult and expensive procedure. A noninvasive diagnostic method which provides molecular information about this bacterial biofilm would foster significant improvements in endocarditis detection and treatment. Ultrasound imaging has unique advantages in terms of availability, cost and portability and in addition provides molecular imaging capabilities in conjunction with targeted ultrasound contrast agents. These agents are encapsulated gas which selectively bind to specific diseased tissue with unique scattering characteristics as they oscillate nonlinearly in an acoustic field, faciltiating the detection and imaging of the targets. We seek to develop a targeted molecular imaging method for the bacterial biofilms associated with endocarditis; however, some preliminary, exploratory investigations are needed to advance this novel area of ultrasound contrast aided imaging. We seek to investigate in a stationary, ambient fluid a) attachment to biofilms of antibodies-targeted ultrasound contrast agents, b) the acoustic scattering as a function of the binding and acoustic parameters, and c) the effect of bacteria viability on the acoustic scattering signatures. Future clinical success depends on the robustness of the binding on the valves and the acoustic scattering signals subject to blood flow. Therefore, we will also investigate the binding and acoustic scattering for physiologically relevant situations and anatomy (continuous flow, different binding surfaces) having similarity to heart valves.