Detecting and Monitoring Implant Infection Using X-ray Excited Luminescence Chemical Imaging (XELCI)

摘要 在美国医院获得的200万例感染中，约有一半与植入的 医疗器械植入医疗器械表面的细菌定植是器械失效的主要原因 并且通常需要移除装置并进行长期抗生素治疗。发病/死亡风险 手术和长期住院使早期发现至关重要。然而，检测具有挑战性， 在出现全身感染症状之前的早期阶段，当细菌局限于难以接近的 植入物的区域。我们将开发一种新的医学成像技术，X射线激发发光化学 XELCI成像技术用于非侵入性检测和监测修饰的植入物表面上的细菌生物膜。我们漫长 长期目标是开发一种检测和监测体内感染的传感器。这种方法是创新的，因为没有 其它成像技术以高分辨率通过厚组织提供表面特异性化学信息。 XELCI是一种扫描光学显微镜，其中窄X射线束照射放射性发光膜 在植入物表面上产生具有pH依赖性光谱的局部发光点。虽然 当发光在“远场”中穿过组织时，其散射和模糊，光谱取决于 发光源的局部pH值，图像分辨率由X射线束宽度定义。我们将 应用该技术检测生物膜下的酸中毒，以检测和监测感染。我们两 具体目标是：1）在体外和离体条件下优化和验证XELCI传感器; 2）使用XELCI评估pH 在兔子模型中愈合和感染期间的变化。这项研究意义重大，因为它 开发了一种非侵入性的方法来检测，监测和原位研究生物膜，最终有可能 降低植入物感染的发病率、死亡率和相关成本。

Abstract Approximately half of the two million infections acquired at hospitals in the US are associated with implanted medical devices. Bacterial colonization of implanted medical device surfaces is a major cause of device failure and usually requires device removal coupled with long term antibiotic treatment. Risks of morbidity/mortality from surgery and prolonged hospitalization make early detection critical. However, detection is challenging at early stages prior to development of systemic symptoms of infection when bacteria localized to inaccessible regions of the implant. We will develop a novel medical imaging technique, X-ray excited luminescent chemical imaging (XELCI) to non-invasively detect and monitor bacterial biofilms on modified implant surfaces. Our long term goal is to develop a sensor to detect and monitor in vivo infection. The approach is innovative because no other imaging technique provides surface-specific chemical information at high-resolution through thick tissue. XELCI is a type of scanning optical microscopy wherein a narrow X-ray beam irradiates a radioluminescent film on the implant surface creating a local luminescent spot with pH -dependent spectra. Although the luminescence scatters and blurs as it passes through the tissue in the “far field,” the spectrum depends upon the local pH at the luminescence source, and image resolution is defined by the X-ray beam width. We will apply the technique to detect acidosis beneath biofilms in order to detect and monitor infection. Our two specific aims are to 1) Refine and validate XELCI sensors in vitro and ex vivo; 2) Use XELCI to Assess pH Changes during Healing and Infection in a Rabbit Model. The proposed research is significant because it develops a non-invasive method to detect, monitor, and study biofilms in situ with the ultimate potential for reducing morbidity, mortality and associated cost from implant infections.