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Oral Cancer Diagnosis with Optical Coherence Tomography. Shu-Fan Chen, Chih-Wei Lu, Meng-Tsan Tsai, Yih-Ming Wang, and C. C. Yang. Graduate Institute ...

Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference Shanghai, China, September 1-4, 2005

Oral Cancer Diagnosis with Optical Coherence Tomography Shu-Fan Chen, Chih-Wei Lu, Meng-Tsan Tsai, Yih-Ming Wang, and C. C. Yang Graduate Institute of Electro-Optical Engineering and Department of Electrical Engineering, National Taiwan University, 1, Roosevelt Road, Section 4, Taipei, Taiwan, R.O.C. (Phone) 886-2-23657624 (Fax) 886-2-23652637 (E-mail) [email protected] Chun-Ping Chiang Department of Dentistry, National Taiwan University, Taipei, Taiwan, R.O.C. Abstract -- We use an optical coherence tomography system with a specially designed probe to image the structures of tissues within the oral cavity for the diagnosis of oral precancer and cancer. Various types of oral mucosa, such as gingiva and buccal mucosa, normal and abnormal, can be well distinguished. Keywords: optical coherence tomography, oral precancer and cancer, scanning probe I. Introduction Oral cancer occurs with an annual incidence of approximately 19,400 cases in the United States [1] and is the fifth most common cancer in the world [2]. In Taiwan, the annual incidence of oral cancers was 3591 (men, 3230; women, 361), accounting for 5.8% of all malignancies in both sexes in 2001. In addition, oral cancers rank as the seventh most prevalent cancer in both sexes and account for the fourth most common cancers in males in 2001 [3]. The main etiologies of oral squamous cell carcinoma (SCC) in Taiwan are areca quid (AQ) chewing, cigarette smoking, and alcohol consumption. In Taiwan, there are two million people who habitually chew AQs [4]; approximately 80% of all oral cancer deaths are associated with this habit [5]. Although treatment modalities including radical surgical excision, chemotherapy and radiotherapy or a combination of surgery and chemotherapy or radiotherapy have been used for oral cancer patients, the 5-year survival rate for oral cancer patients in Taiwan is still very low [6]. The low 5-year survival rate indicates the importance of early diagnosis and early treatment. SCC is the most common type of oral carcinoma. It accounts for about nine of every ten oral malignancies. A majority of oral cancers are found to develop from oral premalignant lesions such as leukoplakia, erythroplakia, erythroleukoplakia, dysplasia, and carcinoma in situ. The malignant transformation rates of oral premalignant lesions are reported to be 1-7% for homogenous, thick leukoplakia, 4-15% for granular or verruciform leukoplakia, 18-47% for erythroleukoplakia, 4-11%

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for moderate dysplasia, and 20-35% for severe dysplasia [7]. The high malignant transformation rates for oral premalignant lesions also indicate the importance of early diagnosis and early treatment. In addition, these oral premalignant lesions are not homogeneous lesions, i.e., some part of the lesion may show only hyperkeratosis and acanthosis, while others may show epithelial dysplasia, carcinoma in situ, or invasive carcinoma. Therefore, one lesion may need multiple biopsies to avoid misdiagnosis of the most severe part of the lesion. To reduce the patients’ suffering from multiple biopsies, one of the best non-invasive ways to help us to choose the most appropriate site for biopsy is to use the optic coherence tomography (OCT) to detect oral precancers and cancers. By using interferometric cross-correlation techniques to detect the coherent backscattered components of short coherence length light, OCT has become a powerful tool for the diagnoses of various diseases [8-10]. Pioneered by Fujimoto and co-workers to perform in vivo clinical imaging of the human eye [11], OCT has been an emerging bio-imaging technology that promises to have broad and significant impact on clinical diagnostic imaging. In this paper, we report the investigation of OCT in vivo imaging of the tissue structure in the oral cavity. We perform OCT imaging on normal and abnormal oral mucosa. The results indicate that OCT is capable of high-resolution imaging for oral precancer and cancer diagnoses. II. OCT System and the Scanning Probe To perform OCT imaging of oral mucosa, we use a compact, fiber-based OCT system, as shown in Fig. 1. The superluminescent diode operating at 950 nm with 65nm bandwidth serves as the light source, producing 1.5 mW in power. The operation of the stepper motor in the scanning probe is completely automated and controlled by a personal computer. Single transverse scan for 1 mm can be finished in 0.2 seconds. Fast depth scanning (penetration into the tissue) is achieved with an optical phase delay line in the reference arm. The in-depth resolution of the OCT system is around 7 Pm. To facilitate the access

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to the tissues in the oral cavity, we construct a specialized L-shaped and a line-shaped probe with linear motors. It is quite convenient for us to probe any area of oral mucosa. The probe pictures are shown in Figs. 2 and 3. The lengths of the scanning probes are around 10 cm. SLD

A/D Converter

Data Processing and Image Construction

LP

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'O= 65 nm Beam splitter with fiber pigtails

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Optical phase delay

Fig. 4 OCT image of the gingival mucosa. The epithelium (EP) appears as the 170 Pm top layer above the 280 µm thick lamina propria (LP).

Probe

An OCT image of one kind of lining mucosa, buccal mucosa, is shown in Fig. 5. Lining mucosa differs structurally from the masticatory one. Besides, we can see the submucosa and connective tissue clearly. The thickness of epithelium (EP) is around 220 Pm, and lamina propria (LP) is 240 Pm. The LP smoothly passes into the submucosa, which is well developed for 500 Pm in depth. The total depth of OCT imaging in the buccal mucosa is 900 Pm.

Sample

Fig. 1 The used OCT system for oral cavity scan.

Fig. 2 The L-shaped scanning probe. The length is around 10 cm and the width is around 2.7 cm.

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1 mm Fig. 3 The line-shaped scanning probe. The length is around 10cm and the width is around 1.7 cm.

Fig. 5. OCT image of the buccal mucosa. The epithelium (EP) appears as the 220 Pm top layer.

III. OCT Scanning Images The oral mucosa can be divided into three types: the masticatory mucosa (gingival and hard palate mucosa), the lining mucosa (alveolar, soft palate, labial, and buccal mucosa, as well as the mucosa of the mouth floor and the ventral surface of the tongue), and the specialized mucosa (lips, dorsum of the tongue). An OCT image of one type of masticatory mucosa, gingival mucosa, is shown in Fig. 4. The submucosa is not clear here and the 170 µm thick layer at the top of the tissue is referred as epithelium (EP), including the keratin layer. The 280 µm thick region beneath the epithelium is the lamina propria (LP). The layer beneath lamina propria is submucosa. The total depth of OCT imaging in the gingival mucosa is 700 Pm.

Figure 6 shows another OCT image of gingival mucosa with the line-shaped probe. The 180~200 µm thick layer at the top of the tissue corresponds to the epithelium, including the keratin layer. The 270~300 µm thick region beneath the epithelium is the lamina propria. Certain structures of submucosa below the lamina propria can also be seen. The OCT system and the probes have been installed in the National Taiwan University Hospital for clinical trials. Quite a few patients have been scanned in their oral cavities with the OCT system and the probes. Fig. 7 shows the OCT scanning images from an oral cancer patient. Here, part (a) shows an image of healthy tissue near the cancerous portion. In the healthy tissue, the layers of EP and LP can be clearly identified. Part (b) shows an image of the cancerous portion, and part (c) illustrates a

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picture of the cancerous portion. The white line in the picture rough indicates the OCT scan location. In Fig. 7(b), the strong backscattered portion, as indicated with an arrow, is identified as the cancer lesion of the volunteer patient. In this portion, the LP layer becomes thicker, from 100 to 200 Pm, implying that the cancer is still in its early stage. The thickness of the cancerous LP layer is supposed to be the useful information for cancer diagnosis. Such information cannot be obtained from surface observation. IV. Conclusions We have demonstrated the OCT system and the probes for oral cavity scanning. The imaging results show the capability of the diagnoses of oral precancer and cancer. This system has been delivered to National Taiwan University Hospital for scanning the volunteers. The details of the diagnosis results for oral precancer and cancer will be presented.

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5. H. W. Kwan, “A statistical study on oral carcinomas in Taiwan with emphasis on the relationship with betel nut chewing: a preliminary report,” J. Formos Med Assoc. 75, 497-505, 1976. 6. Y. K. Chen, H. C. Huang, L. M. Lin, C. C. Lin, “Primary oral squamous cell carcinomas:an analysis of 703 cases in southern Taiwan,” Oral Oncol 35, 173-179, 1999. 7. B. W. Neville, D. D. Damm, C. M. Allen, and J. E. Bouquot, “Epithelial Pathology,“ In: Oral Maxillofacial Pathology, pp. 259-321, W. B. Sauders, Philadelphia, PA, U.S.A. 1995. 8. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical Coherence Tomography," Science, 254, 1178, 1991. 9. M. R. Lee, J. A. Izatt, E. A. Swanson, D. Huang, J. S. Schumun, C. P. Lin, C. A. Puliafito, and J. G. Fujimoto, IEEE Eng. Med. Biol. Mag. 14, 67, 1995. 10. J. G. Fujimoto, M. E. Brezinski, G. T. Tearney, S. A. Boppart, B. E. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, "Biomedical imaging and optical biopsy using optical coherence tomography," Nature Medicine, 1, 970-972, 1995. 11. C. A. Puliafito, M. R. Hee, J. S. Schuman, and J. G. Fujimoto, “Optical Coherence Tomography of Ocular Diseases”, SLACK, Thorofare, NJ, 1996.

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Fig. 6 OCT image of the gingival mucosa. The epithelium (EP) appears as the 180~200 Pm top layer. Acknowledgement This research was supported by National Health Research Institute, The Republic of China, under the grant of NHRI-EX94-9220EI. References: 1. A. Jemal, T. Murray, A. Samuels, et al., “Cancer statistics 2003,” CA Cancer J Clin. 53, 5-26, 2003. 2. M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr Opin Oncol. 13, 176-182, 2001. 3. Cancer registry annual report in Taiwan area, 2001. Department of Health, The Executive Yuan, ROC, November, 2004. 4. Y. C. Ko, Y. L. Huang, C. H. Lee, M. J. Chen, L. M. Lin, C. C. Tsai, “Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan,” J Oral Pathol Med. 24, 450-453, 1995.

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5.7 x 1.2 mm Cancer

(c) Fig. 7 OCT scanning images from an oral cancer patient: (a) an image of healthy tissue near the cancerous portion; (b) an image of the cancerous portion; and (c) a picture of the cancerous portion. The white line in the picture rough indicates the OCT scan location.

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