Integration of Raman Spectroscopy and Optical Coherence Tomography (RS-OCT) for In-Vivo Identification of Bacterial Otitis Media

项目总结 中耳炎(中耳感染)是一种高度流行的疾病，尤其是在幼儿中。一直以来 有记录表明，超过75%的儿童在3岁前至少会有一次中耳炎(OM)发作，以及 许多儿童会有复发性或慢性OM。在大多数情况下，耳朵感染的诊断是基于 在耳镜下观察鼓膜的出现和液体的存在。在缺乏方法的情况下 为了识别细菌感染，在没有确切知识的情况下开出广谱抗生素 I)是否存在活动性感染，以及ii)是否为细菌感染(与病毒感染相比)。既往临床 数据还表明，抗生素治疗只对三分之一的OM患者有效，三分之二的病例有效 可能是由抗生素耐药细菌引起的，或者更有可能是病毒病原体引起的，导致错误的费用 每年超过7亿美元。因此，显然迫切需要一种就诊诊断方法。 一种工具，用于确定是否存在活动性感染，以及感染是否源于细菌。此外，如果我们 可以区分存在的细菌种类，可以不必要地使用广谱抗生素 消除，从而提高对这一高度流行疾病的治疗和管理效果。这 一项提案寻求通过发展集成拉曼光谱-光学相干来满足这一未得到满足的需求 体层摄影术(RSOCT)实时检测和细菌分化的病原微生物 中耳。提出的研究的科学前提是OCT可用于图像引导 RS探针梁的放置，以及任何附着在鼓膜上的生物膜的可视化 这可能表明是细菌感染。该成像系统将与拉曼光谱相结合。 通过确定引起OM的细菌的存在，更直接地评估任何生物膜和/或渗出物 以及通过它的生物化学指纹进行物种形成。该项目的总体目标将通过以下方式实现 技术的创新和融合，随之而来的是一系列系统的体外、体外、体内人体 研究以严谨的数据分析方法勾勒出具体目标。这项研究将具有深远的意义 对我们诊断和护理这些常见的耳朵感染的方式产生了影响。最重要的是，这个项目将提供 关键数据(识别特定细菌种类)，以监测抗生素耐药性的发展，以减少 过度使用抗生素，并最终有效地改善患者的健康。

PROJECT SUMMARY Otitis media (middle ear infection) is a highly prevalent disease, especially in young children. It has been documented that more than 75% of children will have at least one episode of otitis media (OM) by age 3, and many children will have recurrent or chronic OM. In most cases, diagnosis of an ear infection is performed based on the appearance of the tympanic membrane and presence of fluid via an otoscope. In the absence of a method to identify bacterial infections, broad-spectrum antibiotics are prescribed without definitive knowledge of whether i) an active infection present, and ii) whether it is a bacterial infection (versus a viral infection). Previous clinical data also suggests that antibiotic therapy is only effective for one-third of OM patients, with two thirds of cases likely caused by antibiotic resistant bacteria, or more likely, viral pathogens, resulting in a misdirected expense of more than $700 million, annually. Therefore, there is a clear and urgent need for a point-of-care diagnostic tool to determine the presence of an active infection and whether an infection is bacterial in origin. Further, if we can distinguish the bacterial species present, unnecessary administration of broad-spectrum antibiotics can be eliminated, thus improving the efficacy of treatment and management of this highly prevalent disease. This proposal seeks to fulfill this unmet need by developing integrated Raman Spectroscopy-Optical Coherence Tomography (RSOCT) for the real-time detection and bacterial differentiation of pathological microorganisms in the middle ear. The scientific premise of the proposed research is that OCT can be used for image-guided placement of the RS probing beam, as well as visualization of any biofilm affixed to the tympanic membrane which would be indicative of a bacterial infection. This imaging system will be coupled with Raman spectroscopy for a more direct assessment of any biofilm and/or effusion by determining the presence of OM-causing bacteria and speciation via its biochemical fingerprint. The overall objective of the project will be accomplished by technological innovation and integration, followed by a series of systematic in vitro, ex vivo, and in vivo human studies with rigorous data analysis methods outlined in the specific aims. This research will have a profound impact on how we diagnose and care for these common ear infections. Most importantly, this project will provide critical data (identifying specific bacterial species) to monitor the development of antibiotic resistance, to reduce the overuse of antibiotics, and ultimately, to efficiently improve the health of patients.