TARGETED ULTRASOUND CONTRAST ASSISTED IMAGING OF BACTERIAL ENDOCARDITIS

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 心内膜炎通常伴随着被称为心脏瓣膜上的赘生物的生物膜的形成。心内膜炎的死亡率可高达70%，因为治疗通常仅限于静脉注射抗生素或手术。可能需要延长抗生素治疗。 此外，心内膜炎的瓣膜移除和置换是困难且昂贵的手术。一种非侵入性的诊断方法，提供有关这种细菌生物膜的分子信息，将促进心内膜炎的检测和治疗的显着改善。超声成像在可用性、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结合的分子成像能力。这些试剂是封装的气体，当它们在声场中非线性振荡时，它们以独特的散射特性选择性地结合到特定的患病组织，从而促进目标的检测和成像。我们寻求开发一种针对心内膜炎相关细菌生物膜的靶向分子成像方法;然而，需要一些初步的探索性研究来推进超声造影辅助成像的这一新领域。我们试图研究在一个固定的，周围的流体a）附着到生物膜的抗体靶向的超声造影剂，B）的声散射作为一个函数的结合和声学参数，和c）的影响细菌的生存能力上的声散射签名。未来的临床成功取决于瓣膜上的结合的稳健性和受血流影响的声散射信号。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.