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A feasibility study of using fiber-optic Raman spectrum system for fast diagnosis of gastric cancer
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摘要:
本文提出了一种能够与胃镜相匹配的光纤拉曼光谱系统和积分能量比相结合来快速诊断胃癌的方法。首先，采用光纤拉曼光谱系统对来自17例胃正常粘膜，12例胃腺癌粘膜的活检组织进行拉曼光谱检测(激发光波长785 nm，功率50 mW, CCD温度-80 ℃，采集时间1 s)。然后，采用降低基线、快速傅里叶转化(FFT)平滑对拉曼原始光谱进行预处理。最后，根据拉曼谱图特征，分析了拉曼特征峰的归属，比较了胃正常和胃腺癌粘膜的拉曼光谱差异和连续频带内(1500 cm-1~1700 cm-1)和非连续频带(1100 cm-1~1200 cm-1)积分能量比。结果表明，胃腺癌粘膜位于1002 cm-1、1073 cm-1、1450 cm-1、1655 cm-1归属于苯丙氨酸和蛋白质的拉曼峰强度比正常粘膜相对增高，胃正常和胃腺癌粘膜在连续频带内和非连续频带积分能量差异明显(独立样本t检验，P < 0.05)，并以积分能量的比值来作为诊断指标，获得的准确度达到97.5%~98.5%，敏感度达到91.7%和特异度达到100.0%。
Abstract:A method for fast diagnosing gastric cancer is proposed, by combining optical fiber Raman spectroscopy system matching the gastroscope with the ratios of the spectral integral energy. we complete the detecting of Raman spectra from 17 samples of normal gastric mucosa and 12 samples of gastric adenocarcinoma mucosa using the optical fiber Raman spectroscopy system (excitation wavelength of 785 nm light, power of 50 mW, the CCD temperature to 80 ℃, acquisition time 1 s). Then, the original Raman spectra were pretreated, through reducing the baseline and smoothing by fast Fourier transformation (FFT). Finally, according to the characters of Raman spectra, Raman characteristic peaks were analyzed. At the same time, we compared the ratio of integral energy of continuous band (1500 cm-1~1700 cm-1) and non-continuous band (1100 cm-1~1200 cm-1). The results show that the intensity of Raman peak of gastric adenocarcinoma at 1002 cm-1、1073 cm-1、1450 cm-1、1655 cm-1 belonging to phenylalanine and proteins are higher than that of normal mucosal relatively. From continuous band (1500 cm-1~ 1700 cm-1) and non-continuous band (1100 cm-1~1200 cm-1), the ratios of the spectral integral energy of gastric adenocarcinoma were different with normal mucosa markedly(independent samples t test, P < 0.05), and with the ratio of the integral energy for use as a diagnostic index, obtained the higher accuracy (97.5%~98.5%), sensitivity (91.7%) and specific degrees (100.0%).
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Key words:
- optical fiber /
- Raman spectrum /
- gastric cancer /
- diagnosis
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Overview: Gastric cancer incidence and mortality is high in China. Because of the lack of specificity, the diagnosis accuracy of gastric cancer is not high. Raman spectroscopy is a kind of inelastic scattering spectroscopy based on molecular vibrations, which can provide specific information of structure and composition of tissue. Cancerous tissue can provide characteristic Raman spectra due to its composition content, structural changes. Raman spectroscopy is very suitable for the diagnosis of gastric cancer. Optical fiber Raman spectroscopy system can be used for real-time diagnosis of gastric cancer. The aim of this study was to structure a fiber Raman spectroscopy system matching the gastroscope and combining with the ratios of the spectral integral energy to diagnosis of gastric cancer fast. We used this system to collected 83 spectrum from 29 patients with biopsy examination, including 17 patients with gastric carcinoma and 12 patients with normal gastric mucosa (excitation wavelength of 785 nm light, power of 50 mW, the CCD temperature to 80 ℃, acquisition time 1 s). Original Raman spectrum contained the weak Raman spectrum of tissue itself we needed, the strong autofluorescence background and noise. By reducing the baseline to remove tissue autofluorescence background and using fast Fourier transform (FFT) to increase signal-to-noise ratio, the original Raman spectrum was preprocessed. And then we got the average spectrum of gastric cancer and normal stomach mucosa tissue respectively and analyzed the ownership of the typical Raman spectrum peak. After standardizing the average spectrum, we calculated the integral energy of Raman spectra. Raman spectrum and the ratio of integral energy from continuous band (1500 cm-1~1700 cm-1) and non-continuous band (1100 cm-1~1200 cm-1) were compared. The intensity of Raman peak of gastric adenocarcinoma at 1002 cm-1、1073 cm-1、1450 cm-1、1655 cm-1. Belonging to phenylalanine and proteins are higher than that of normal mucosal relatively. From continuous band (1500 cm-1~1700 cm-1) and non- continuous band (1100 cm-1~1200 cm-1), the ratios of the spectral integral energy of gastric adenocarcinoma were different with normal mucosa markedly (independent samples t test, P < 0.05), and with the ratio of the integral energy for use as a diagnostic index, obtained the higher accuracy (97.5%~ 98.5%), sensitivity (91.7%) and specific degrees (100.0%). Fiber Raman spectroscopy system applied in the clinical diagnosis of gastric cancer had a high value.
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图 2 (a) 原始拉曼光谱；(b)降低基线、平滑预处理后的拉曼光谱
Figure 2. (a) Original Raman spectrum; (b) Raman spectra after reduced the baseline and smoothed
图 3 17例胃正常患者(蓝线)和12例胃腺癌患者(红线)的平均拉曼光谱
Figure 3. The mean normalized Raman spectra from normal(n=17, blue line) and dysplasia (n=12, red line) gastric mucosa tissue samples
图 4 胃正常和胃癌粘膜拉曼光谱连续频带和非连续频带积分能量比
Figure 4. The ratio of integral energy of continuous and discontinuous frequency band of the Raman spectra
图 5 拉曼光谱连续频带和非连续频带积分能量比的ROC曲线
Figure 5. ROC curve of continuous and discontinuous frequency band of the Raman spectra
表 1 拉曼谱峰振动方式及其归属
Table 1. Vibration mode and ownership of Raman spectrum peak
Raman peak Mode of vibration Ownership 1002 C-C νs Phenylalanine 1073 C-N ν Protein 1206 Phenyl ring ν Protein 1265 Random coil Amide Ⅲ protein 1340 Plane ring ν Protein 1450 C–H2、C–H3 δ Protein、DNA /RNA、lipid Phenyl ring ν 1550 Lipid 1655 α-helix Amide Ⅰ protein Annotation：νs：Symmetrical stretching vibration；ν：Stretching vibration；δ：Bending vibration 
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表 2 拉曼光谱不同频带积分能量比
Table 2. The ratio of integral energy of different frequency band of the Raman spectra
Normal Cancer E2/E1 E2/E3 E2/E1 E2/E3 0.72 0.40 1.25 1.10 0.58 0.44 1.26 0.71 0.60 0.49 1.21 0.97 0.79 0.40 1.43 0.99 0.58 0.67 1.02 1.20 0.64 0.38 0.89 1.08 0.66 0.55 0.71 1.35 0.59 0.35 1.21 1.64 0.64 0.51 0.87 0.79 0.72 0.40 1.20 0.51 0.58 0.41 1.49 0.80 0.85 0.40 1.08 0.72 0.60 0.37 0.81 0.37 0.55 0.35 0.65 0.27 0.66 0.62 Annotation：E1：E1500 cm-1~1600 cm-1；E2：E1600 cm-1~1700 cm-1；E3：E1100 cm-1~1200 cm-1
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