National University of Singapore, Department of Bioengineering, Faculty of Engineering, Singapore.
J Biomed Opt. 2011 Mar;16(3):037003. doi: 10.1117/1.3556723.
Raman spectroscopy is an optical vibrational technology capable of probing biomolecular changes of tissue associated with cancer transformation. This study aimed to characterize in vivo Raman spectroscopic properties of tissues belonging to different anatomical regions in the upper gastrointestinal (GI) tract and explore the implications for early detection of neoplastic lesions during clinical gastroscopy. A novel fiber-optic Raman endoscopy technique was utilized for real-time in vivo tissue Raman measurements of normal esophageal (distal, middle, and proximal), gastric (antrum, body, and cardia) as well as cancerous esophagous and gastric tissues from 107 patients who underwent endoscopic examinations. The non-negativity-constrained least squares minimization coupled with a reference database of Raman active biochemicals (i.e., actin, histones, collagen, DNA, and triolein) was employed for semiquantitative biomolecular modeling of tissue constituents in the upper GI. A total of 1189 in vivo Raman spectra were acquired from different locations in the upper GI. The Raman spectra among the distal, middle, and proximal sites of the esophagus showed no significant interanatomical variability. The interanatomical variability of Raman spectra among normal gastric tissue (antrum, body, and cardia) was subtle compared to cancerous tissue transformation, whereas biomolecular modeling revealed significant differences between the two organs, particularly in the gastroesophageal junction associated with proteins, DNA, and lipids. Cancerous tissues can be identified across interanatomical regions with accuracies of 89.3% [sensitivity of 92.6% (162∕175); specificity of 88.6% (665∕751)], and of 94.7% [sensitivity of 90.9% (30∕33); specificity of 93.9% (216∕230)] in the gastric and esophagus, respectively, using partial least squares-discriminant analysis together with the leave-one tissue site-out, cross validation. This work demonstrates that Raman endoscopy technique has promising clinical potential for real-time, in vivo diagnosis and detection of malignancies in the upper GI at the molecular level.
拉曼光谱是一种光学振动技术，能够探测与癌症转化相关的组织生物分子变化。本研究旨在描述上消化道（GI）不同解剖区域组织的体内拉曼光谱特性，并探讨其在临床胃镜检查中早期检测肿瘤病变的意义。利用一种新型光纤拉曼内窥镜技术，对 107 例接受内镜检查的患者的正常食管（远端、中段和近端）、胃（胃窦、体和贲门）以及癌性食管和胃组织进行实时体内组织拉曼测量。采用非负最小二乘最小化方法，结合拉曼活性生物化学物质（即肌动蛋白、组蛋白、胶原、DNA 和三油酸甘油酯）的参考数据库，对胃上 GI 组织的生物分子进行半定量建模。共从胃上 GI 的不同部位采集了 1189 个体内拉曼光谱。食管远端、中段和近端部位的拉曼光谱无明显解剖学变异性。与癌组织转化相比，正常胃组织（胃窦、体和贲门）的拉曼光谱解剖学变异性较小，而生物分子建模显示两个器官之间存在显著差异，特别是在与蛋白质、DNA 和脂质相关的胃食管交界处。跨解剖区域的癌组织识别准确率为 89.3%（敏感性为 92.6%（162∕175）；特异性为 88.6%（665∕751）），在胃和食管中分别为 94.7%（敏感性为 90.9%（30∕33）；特异性为 93.9%（216∕230）），采用偏最小二乘判别分析结合留一组织部位交叉验证。这项工作表明，拉曼内窥镜技术具有在胃上 GI 进行实时体内诊断和检测恶性肿瘤的临床潜力。
