Dual-wavelength endoscopic Raman probe for eosinophilic esophagitis

项目摘要 嗜酸性食管炎(EoE)是一种影响食道的慢性炎症性疾病，也是最常见的 呕吐、进食和吞咽困难的常见原因，包括儿童食道食物嵌塞。 EoE很难使用白色实时诊断并与其他常见的食道疾病区分开来 通过食管胃十二指肠镜(EGD)程序进行的食管光内窥镜成像。 因此，临床医生依赖于在此过程中获得的多次随机的食道活组织检查 组织学证实(金标准)。然而，由于EoE是一种斑片状疾病，即使多次活检也可能 不会产生准确的结果。这可能导致延误诊断和无效治疗，并导致 可预防的并发症，如需要手术干预的食道重塑。因此，有一种 迫切需要开发替代诊断工具，以快速检查更多的食道区域 并为EoE的实时识别提供组织特异性炎症生物标志物信息。拉曼 光谱(RS)是一种可以提供解决方案的技术，因为它依赖于光与 分子可以提供样品的生物化学和分子组成的独特“指纹” 几秒钟。因此，经内窥镜的RS特别适用于活动期EoE的实时生化评估。 本文介绍了一种深度特定的双波长拉曼激光器的研制和性能评价 内窥镜检查食道内的生化和水分变化，因为它与活动期食管炎有关。 为了实现这些目标，拉曼生物标志物将在空间上进行表征和识别，并与 已知的体内和体外EoE的生物标志物。将使用修改后的 基于组织光学特性的蒙特卡罗模拟优化探头设计。体外非线性成像 结合拉曼图谱将对在EGD过程中获得的活检的子集执行，以 进一步研究关键生物标志物的空间分布，有助于指导内窥镜拉曼探针的设计。这 将使用光学组织模体和体内患者测量来评估探头。最后，一台机器 学习分类算法将被优化和评估，以提供一种在活体RS中使用的机制 光谱可分为活动期EoE、非活动期EoE、GERD(即酸反流病)和其他非EoE 控制力。此外，我们的目标是跟踪患者对治疗的反应，并评估 是时候确定使用RS提供预测性治疗结果模型的可行性了。 这一提议的成功完成将产生一种用于实时检测和监测的新型诊断工具 EoE在儿科病例中的发生率。

Project Summary Eosinophilic esophagitis (EoE) is a chronic inflammatory disease affecting the esophagus, and one of the most common causes of vomiting, feeding and swallowing difficulties, including esophageal food impaction in children. EoE is difficult to diagnose and distinguish from other common esophageal diseases in real-time using white light endoscopic imaging of the esophagus conducted via an esophagogastroduodenoscopy (EGD) procedure. Therefore, clinicians rely on multiple random esophageal biopsies which is obtained during this procedure for histologic confirmation (gold standard). However, since EoE is a patchy disease even the multiple biopsies may not yield accurate results. This can lead to a delay in diagnosis and ineffective treatment, and result in preventable complications such as esophageal remodeling requiring surgical interventions. As such there is an urgent need to develop alternative diagnostic tools which can quickly survey more regions of the esophagus, in situ, and provide tissue-specific inflammatory biomarker information for real-time identification of EoE. Raman spectroscopy (RS) is one such technology that can provide a solution as it relies on light interaction with molecules to provide a unique “fingerprint” of the biochemical and molecular composition of a specimen within seconds. Therefore, RS via an endoscope is uniquely suited for real-time biochemical assessment of active EoE. This proposal, presents the development and assessment of a depth specific dual-wavelength Raman endoscope to characterize both biochemical and water changes within the esophagus as it relates to active EoE. To accomplish these goals, Raman biomarkers will be characterized and identified spatially and correlated with known biomarkers of EoE in vivo as well as ex vivo. Computational modeling will be performed using a modified Monte Carlo simulation to optimize probe design based on tissue optical properties. Ex vivo non-linear imaging coupled with Raman maps will be performed on a subset of biopsies, obtained during the EGD procedures, to further study the spatial distribution of key biomarkers and help guide the endoscopic Raman probe design. This probe will be evaluated using optical tissue phantoms and in vivo patient measurements. Finally, a machine learning classification algorithm will be optimized and evaluated to provide a mechanism by which in vivo RS spectra can be classified into active EoE, inactive EoE, GERD (i.e., acid reflux disease) and other non-EoE control. Furthermore, we aim to track patient’s response to treatment and assess Raman spectral changes over time to determine the feasibility of using RS to provide a predictive treatment outcome model. The successful completion of this proposal will yield a novel diagnostic tool for real-time detection and monitoring of EoE in pediatric cases.