Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117576.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119260.
Theranostics. 2017 Aug 18;7(14):3517-3526. doi: 10.7150/thno.16359. eCollection 2017.
We report the utility of a simultaneous fingerprint (FP) (i.e., 800-1800 cm) and high-wavenumber (HW) (i.e., 2800-3600 cm) fiber-optic Raman spectroscopy developed for real-time diagnosis of nasopharyngeal carcinoma (NPC) at endoscopy. A total of 3731 high-quality FP/HW Raman spectra (normal=1765; cancer=1966) were acquired in real-time from 204 tissue sites (normal=95; cancer=109) of 95 subjects (normal=57; cancer=38) undergoing endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous nasopharyngeal tissues that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in NPC. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with leave-one subject-out, cross-validation (LOO-CV) were implemented to develop robust Raman diagnostic models. The simultaneous FP/HW Raman spectroscopy technique together with PCA-LDA and LOO-CV modeling provides a diagnostic accuracy of 93.1% (sensitivity of 93.6%; specificity of 92.6%) for nasopharyngeal cancer identification, which is superior to using either FP (accuracy of 89.2%; sensitivity of 89.9%; specificity of 88.4%) or HW (accuracy of 89.7%; sensitivity of 89.0%; specificity of 90.5%) Raman technique alone. Further receiver operating characteristic (ROC) analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for diagnosis of NPC. This work demonstrates for the first time that simultaneous FP/HW fiber-optic Raman spectroscopy technique has great promise for enhancing real-time cancer diagnosis in the nasopharynx during endoscopic examination.
我们报告了一种同时使用指纹(FP)(即 800-1800cm)和高波数(HW)(即 2800-3600cm)光纤拉曼光谱技术,用于实时诊断内窥镜检查中的鼻咽癌(NPC)。从 95 名接受内窥镜检查的受试者(正常=57;癌症=38)的 204 个组织部位(正常=95;癌症=109)实时获得了总共 3731 个高质量的 FP/HW 拉曼光谱(正常=1765;癌症=1966)。FP/HW 拉曼光谱在正常和癌性鼻咽组织之间存在显著差异,这归因于 NPC 中蛋白质、脂质、核酸和结合水含量的变化。主成分分析(PCA)和线性判别分析(LDA)以及留一受试者外,交叉验证(LOO-CV)被实施以开发稳健的拉曼诊断模型。同时使用 FP/HW 拉曼光谱技术以及 PCA-LDA 和 LOO-CV 建模提供了 93.1%(敏感性为 93.6%;特异性为 92.6%)的鼻咽癌识别诊断准确性,优于单独使用 FP(准确性为 89.2%;敏感性为 89.9%;特异性为 88.4%)或 HW(准确性为 89.7%;敏感性为 89.0%;特异性为 90.5%)拉曼技术。进一步的接收器操作特性(ROC)分析再次证实了同时使用 FP/HW 拉曼技术诊断 NPC 的最佳性能。这项工作首次证明,同时使用 FP/HW 光纤拉曼光谱技术具有很大的潜力,可以提高内窥镜检查中鼻咽部的实时癌症诊断。