Characterizing Variability of In Vivo Raman Spectroscopic Properties of Different Anatomical Sites of Normal Colorectal Tissue towards Cancer Diagnosis at Colonoscopy
Characterizing Variability of In Vivo Raman Spectroscopic Properties of Different Anatomical Sites of Normal Colorectal Tissue towards Cancer Diagnosis at Colonoscopy
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DOI：
10.1021/ac503287u
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发表时间：
2015-01-20
影响因子：
7.4
通讯作者：
Huang, Zhiwei
中科院分区：
文献类型：
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作者：
Bergholt, Mads Sylvest;Zheng, Wei;Huang, Zhiwei
本研究旨在描述正常大肠组织的体内拉曼光谱特性，并评估结直肠不同解剖位置的独特生物分子变异，以用于癌症诊断。我们研制了一种新型的785 nm激发光纤拉曼内窥镜，它可以同时获取大肠组织亚表面的在体指纹(FP)光谱(8001800 Cm1)和高波数(HW)拉曼光谱(28003600 Cm1)。我们应用FP/HW拉曼内窥镜对50例受试者的大肠不同解剖部位(升结肠182例、横结肠249例、降结肠124例、乙状结肠212例和直肠362例)进行了活体组织拉曼测量。采用偏最小二乘(PLS)-判别分析(DA)评价解剖变异。正常大肠组织在分子组成(即蛋白质、脂肪和水分含量)上表现出微妙的解剖差异，并可分为三大类：(1)升结肠和横结肠，(2)降结肠，(3)乙状结肠和直肠。不同组织部位的敏感性(SE)和特异性(SP)不同(升结肠：SE：1.10%，SP：91.02；横结肠：SE：14.06%，SP：78.78；降结肠：SE：40.32%，SP：81.99；乙状结肠：SE：19.34%，SP：87.90；直肠：SE：71.55%，SP：77.84)。解剖间的分子变异比肿瘤组织转化小一个数量级。进一步对活体FP/HW组织拉曼光谱进行偏最小二乘法建模，诊断结直肠癌的准确率为88.8%(敏感度：93.9%(93/99)；特异度为88.3%(997/1129)。这项工作揭示了正常结直肠组织的解剖间拉曼光谱的变异性与癌组织相比微乎其微，同时FP/HW拉曼内窥镜技术在分子水平的实时活体诊断结直肠癌方面具有潜在的应用前景。
This study aims to characterize the in vivo Raman spectroscopic properties of normal colorectal tissues and to assess distinctive biomolecular variations of different anatomical locations in the colorectum for cancer diagnosis. We have developed a novel 785 nm excitation fiber-optic Raman endoscope that can simultaneously acquire in vivo fingerprint (FP) spectra (8001800 cm1) and high-wavenumber (HW) Raman spectra (28003600 cm1) from the subsurface of colorectal tissue. We applied the FP/HW Raman endoscope for in vivo tissue Raman measurements of various normal colorectal anatomical locations (i.e., ascending colon (n = 182), transverse colon (n = 249), descending colon (n = 124), sigmoid (n = 212), and rectum (n = 362)) in 50 subjects. Partial least-squares (PLS)-discriminant analysis (DA) was employed to evaluate the interanatomical variability. The normal colorectal tissue showed a subtle interanatomical variability in molecular constituents (i.e., proteins, lipids, and water content) and could be divided into three major clusterings: (1) ascending colon and transverse colon, (2) descending colon, and (3) sigmoid and rectum. The PLS-DA multiclass algorithms were able to identify different tissue sites with varying sensitivities (SE) and specificities (SP) (ascending colon: SE: 1.10%, SP: 91.02; transverse colon: SE: 14.06%, SP: 78.78; descending colon: SE: 40.32%, SP: 81.99; sigmoid: SE: 19.34%, SP: 87.90; rectum: SE: 71.55%, SP: 77.84). The interanatomical molecular variability was orders of magnitude less than neoplastic tissue transformation. Further PLS-DA modeling on in vivo FP/HW tissue Raman spectra yielded a diagnostic accuracy of 88.8% (sensitivity: 93.9% (93/99); specificity 88.3% (997/1129) for colorectal cancer detection. This work discloses that interanatomical Raman spectral variability of normal colorectal tissue is subtle compared to cancer tissue, and the simultaneous FP/HW Raman endoscopic technique has promising potential for real-time, in vivo diagnosis of colorectal cancer at the molecular level.