Journal Home Online First Current Issue Archive For Authors Journal Information 中文版

Engineering >> 2015, Volume 1, Issue 3 doi: 10.15302/J-ENG-2015081

A Confocal Endoscope for Cellular Imaging

1 Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China
2 MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
3 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China

Received: 2015-08-05 Revised: 2015-09-06 Accepted: 2015-09-10 Available online: 2015-09-30

Next Previous

Abstract

Since its inception, endoscopy has aimed to establish an immediate diagnosis that is virtually consistent with a histologic diagnosis. In the past decade, confocal laser scanning microscopy has been brought into endoscopy, thus enabling in vivo microscopic tissue visualization with a magnification and resolution comparable to that obtained with the ex vivo microscopy of histological specimens. The major challenge in the development of instrumentation lies in the miniaturization of a fiber-optic probe for microscopic imaging with micron-scale resolution. Here, we present the design and construction of a confocal endoscope based on a fiber bundle with 1.4-μm lateral resolution and 8-frames per second (fps) imaging speed. The fiber-optic probe has a diameter of 2.6 mm that is compatible with the biopsy channel of a conventional endoscope. The prototype of a confocal endoscope has been used to observe epithelial cells of the gastrointestinal tracts of mice and will be further demonstrated in clinical trials. In addition, the confocal endoscope can be used for translational studies of epithelial function in order to monitor how molecules work and how cells interact in their natural environment.

Figures

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig.6

Fig. 7

Fig. 8

Fig. 9

Fig. 10

Fig. 11

Fig. 12

References

[ 1 ] B. Stewart, C. P. Wild. World Cancer Report 2014. Geneva: World Health Organization, 2014

[ 2 ] T. A. Stamey, N. Yang, A. R. Hay, J. E. McNeal, F. S. Freiha, E. Redwine. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N. Engl. J. Med., 1987, 317(15): 909–916

[ 3 ] J. M. Edmonson. History of the instruments for gastrointestinal endoscopy. Gastrointest. Endosc., 1991, 37(Suppl. 2): S27–S56 link1

[ 4 ] B. I. Hirschowitz, C. W. Peters, L. E. Curtiss. Preliminary report on a long fiberscope for examination of stomach and duodenum. Med. Bull. (Ann Arbor), 1957, 23(5): 178–180

[ 5 ] B. I. Hirschowitz. A personal history of the fiberscope. Gastroenterology, 1979, 76(4): 864–869

[ 6 ] J. Pohl, Comparison of computed virtual chromoendoscopy and conventional chromoendoscopy with acetic acid for detection of neoplasia in Barrett’s esophagus. Endoscopy, 2007, 39(7): 594–598 link1

[ 7 ] ASGE Technology Committee; L. M. Wong Kee Song, Chromoendoscopy. Gastrointest. Endosc., 2007, 66(4): 639–649 link1

[ 8 ] K. K. Wang, N. Okoro, G. Prasad, M. Wong Kee Song, N. S. Buttar, J. Tian. Endoscopic evaluation and advanced imaging of Barrett’s esophagus. Gastrointest. Endosc. Clin. N. Am., 2011, 21(1): 39–51 link1

[ 9 ] R. Kiesslich, Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology, 2004, 127(3): 706–713 link1

[10] M. Goetz, N. P. Malek, R. Kiesslich. Microscopic imaging in endoscopy: Endomicroscopy and endocytoscopy. Nat. Rev. Gastroenterol. Hepatol., 2014, 11(1): 11–18

[11] A. Meining, Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: A multicenter experience. Gastrointest. Endosc., 2011, 74(5): 961–968 link1

[12] T. Liu, H. Zheng, W. Gong, C. Chen, B. Jiang. The accuracy of confocal laser endomicroscopy, narrow band imaging, and chromoendoscopy for the detection of atrophic gastritis. J. Clin. Gastroenterol., 2015, 49(5): 379–386 link1

[13] M. Goetz. Endomicroscopy and targeted imaging of gastric neoplasia. Gastrointest. Endosc. Clin. N. Am., 2013, 23(3): 597–606 link1

[14] L. Ginlünas, R. Juškaitis, S. V. Shatalin. Scanning fibre-optic microscope. Electron. Lett., 1991, 27(9): 724–726 link1

[15] M. Gu, C. J. R. Sheppard, X. Gan. Image formation in a fiber-optical confocal scanning microscope. J. Opt. Soc. Am. A, 1991, 8(11): 1755–1761

[16] S. Kimura, T. Wilson. Confocal scanning optical microscope using single-mode fiber for signal detection. Appl. Opt., 1991, 30(16): 2143–2150 link1

[17] A. F. Gmitro, D. Aziz. Confocal microscopy through a fiber-optic imaging bundle. Opt. Lett., 1993, 18(8): 565–567 link1

[18] M. B. Wallace, P. Fockens. Probe-based confocal laser endomicroscopy. Gastroenterology, 2009, 136(5): 1509–1513 link1

[19] R. Kiesslich, M. Goetz, M. Vieth, P. R. Galle, M. F. Neurath. Technology insight: Confocal laser endoscopy for in vivo diagnosis of colorectal cancer. Nat. Clin. Pract. Oncol., 2007, 4(8): 480–490 link1

[20] M. Goetz, A. Watson, R. Kiesslich. Confocal laser endomicroscopy in gastrointestinal diseases. J. Biophotonics, 2011, 4(7−8): 498–508 link1

[21] J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner. Endoscope-compatible confocal microscope using a gradient index-lens system. Opt. Commun., 2001, 188(5−6): 267–273 link1

[22] J. C. Jung, M. J. Schnitzer. Multiphoton endoscopy. Opt. Lett., 2003, 28(11): 902–904 link1

[23] A. R. Rouse, A. Kano, J. A. Udovich, S. M. Kroto, A. F. Gmitro. Design and demonstration of a miniature catheter for a confocal microendoscope. Appl. Opt., 2004, 43(31): 5763–5771 link1

[24] C. Liang, K. B. Sung, R. R. Richards-Kortum, M. R. Descour. Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope. Appl. Opt., 2002, 41(22): 4603–4610 link1

[25] M. D. Chidley, K. D. Carlson, R. R. Richards-Kortum, M. R. Descour. Design, assembly, and optical bench testing of a high-numerical-aperture miniature injection-molded objective for fiber-optic confocal reflectance microscopy. Appl. Opt., 2006, 45(11): 2545–2554 link1

[26] R. T. Kester, T. Christenson, R. R. Kortum, T. S. Tkaczyk. Low cost, high performance, self-aligning miniature optical systems. Appl. Opt., 2009, 48(18): 3375–3384 link1

[27] M. Kyrish, Needle-based fluorescence endomicroscopy via structured illumination with a plastic, achromatic objective. J. Biomed. Opt., 2013, 18(9): 096003 link1

[28] W. Piyawattanametha, In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror. Opt. Lett., 2009, 34(15): 2309–2311 link1

[29] J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, J. N. Kerr. Visually evoked activity in cortical cells imaged in freely moving animals. Proc. Natl. Acad. Sci. U.S.A., 2009, 106(46): 19557–19562 link1

[30] J. Sawinski, W. Denk. Miniature random-access fiber scanner for in vivo multiphoton imaging. J. Appl. Phys., 2007, 102(3): 034701

[31] Y. Zhang, A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy. Proc. Natl. Acad. Sci. U.S.A., 2012, 109(32): 12878–12883 link1

[32] C. M. Lee, C. J. Engelbrecht, T. D. Soper, F. Helmchen, E. J. Seibel. Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging. J. Biophotonics, 2010, 3(5−6): 385–407 link1

[33] B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer. Fiber-optic fluorescence imaging. Nat. Methods, 2005, 2(12): 941–950 link1

[34] Z. Li, Z. Yang, L. Fu. Scanning properties of a resonant fiber-optic piezoelectric scanner. Rev. Sci. Instrum., 2011, 82(12): 123707 link1

[35] Z. Li, L. Fu. Note: A resonant fiber-optic piezoelectric scanner achieves a raster pattern by combining two distinct resonances. Rev. Sci. Instrum., 2012, 83(8): 086102 link1

[36] R. Sjöback, J. Nygren, M. Kubista. Absorption and fluorescence properties of fluorescein. Spectrochim. Acta A Mol. Biomol. Spectrosc., 1995, 51(6): L7–L21 link1

[37] V. K. Sharma, P. D. Sahare, R. C. Rastogi, S. K. Ghoshal, D. Mohan. Excited state characteristics of acridine dyes: Acriflavine and acridine orange. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2003, 59(8): 1799–1804 link1

[38] A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, P. M. Delaney. A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest. Endosc., 2005, 62(5): 686–695 link1

[39] J. M. Jabbour, M. A. Saldua, J. N. Bixler, K. C. Maitland. Confocal endomicroscopy: Instrumentation and medical applications. Ann. Biomed. Eng., 2012, 40(2): 378–397 link1

[40] S. C. Park, M. K. Park, M. G. Kang. Super-resolution image reconstruction: A technical overview. IEEE Signal Proc. Mag., 2003, 20(3): 21–36 link1

[41] S. Lertrattanapanich, N. K. Bose. High resolution image formation from low resolution frames using Delaunay triangulation. IEEE Trans. Image Process., 2002, 11(12): 1427–1441 link1

[42] T. Kuiper, New classification for probe-based confocal laser endomicroscopy in the colon. Endoscopy, 2011, 43(12): 1076–1081 link1

[43] M. Goetz, In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by targeting epidermal growth factor receptor. Gastroenterology, 2010, 138(2): 435–446 link1

[44] D. Moussata, Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo. Gut, 2011, 60(1): 26–33 link1

[45] Y. Goto, H. Kiyono. Epithelial barrier: An interface for the cross-communication between gut flora and immune system. Immunol. Rev., 2012, 245(1): 147–163 link1

[46] S. Foersch, et al. Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy. Gut, 2010, 59(8): 1046–1055 link1

Related Research