Endoscopic Microscopy

In vivo endoscopic optical microscopy provides a tool to assess tissue architecture and morphology with contrast and resolution similar to that provided by standard histopathology – without need for physical tissue removal. In this article, we focus on optical imaging technologies that have the potential to dramatically improve the detection, prevention, and therapy of epithelial cancers. Epithelial pre-cancers and cancers are associated with a variety of morphologic, architectural, and molecular changes, which currently can be assessed only through invasive, painful biopsy. Optical imaging is ideally suited to detecting cancer-related alterations because it can detect biochemical and morphologic alterations with sub-cellular resolution throughout the entire epithelial thickness. Optical techniques can be implemented non-invasively, in real time, and at low cost to survey the tissue surface at risk. Our manuscript focuses primarily on modalities that currently are the most developed: reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). However, recent advances in fluorescence-based endoscopic microscopy also are reviewed briefly. We discuss the basic principles of these emerging technologies and their current and potential applications in early cancer detection. We also present research activities focused on development of exogenous contrast agents that can enhance the morphological features important for cancer detection and that have the potential to allow vital molecular imaging of cancer-related biomarkers. In conclusion, we discuss future improvements to the technology needed to develop robust clinical devices.

[1]  U Seitz,et al.  In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus. , 2000, Endoscopy.

[2]  Y. Sabharwal,et al.  Slit-scanning confocal microendoscope for high-resolution in vivo imaging. , 1999, Applied optics.

[3]  T Wilson,et al.  Direct-view fiber-optic confocal microscope. , 1994, Optics letters.

[4]  B Messerschmidt,et al.  Endoscope-compatible confocal microscope using a gradient index-lens system , 2001 .

[5]  A. Halpern,et al.  Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy. , 2001, Archives of dermatology.

[6]  D Fujimoto,et al.  Isolation and characterization of a fluorescent material in bovine achilles tendon collagen , 1977 .

[7]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. , 1995, The Journal of investigative dermatology.

[8]  A. Fercher,et al.  Dynamic coherent focus OCT with depth-independent transversal resolution , 1999 .

[9]  M. Rajadhyaksha,et al.  Elucidating the pulsed-dye laser treatment of sebaceous hyperplasia in vivo with real-time confocal scanning laser microscopy. , 2000, Journal of the American Academy of Dermatology.

[10]  A J Welch,et al.  Sources of contrast in confocal reflectance imaging. , 1996, Applied optics.

[11]  David A. Jackson,et al.  OCT en-face images from the retina with adjustable depth resolution in real time , 1999 .

[12]  Raghavan Rajagopalan,et al.  New approach to optical imaging of tumors , 2001, SPIE BiOS.

[13]  J.Edward Hall,et al.  Diagnostic cytology and its histopathologic Bases , 1962 .

[14]  S. Yazdanfar,et al.  An Optical Coherence Microscope for 3-dimensional Imaging in Developmental Biology References and Links , 2022 .

[15]  Wolfgang Rudolph,et al.  Comparative study of confocal and heterodyne microscopy for imaging through scattering media , 1996 .

[16]  Allen Taflove,et al.  Computational Electrodynamics the Finite-Difference Time-Domain Method , 1995 .

[17]  Harald Sattmann,et al.  A thermal light source technique for optical coherence tomography , 2000 .

[18]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[19]  M. Manfait,et al.  Selective analysis of antitumor drug interaction with living cancer cells as probed by surface-enhanced Raman spectroscopy , 2004, European Biophysics Journal.

[20]  R. Richards-Kortum,et al.  Metal nanoparticles as biospecific contrast agents for cancer imaging , 2002 .

[21]  J. Schwartz Biomarkers and molecular epidemiology and chemoprevention of oral carcinogenesis. , 2000, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[22]  R. Anderson,et al.  Confirmation of onychomycosis by in vivo confocal microscopy. , 2000, Journal of the American Academy of Dermatology.

[23]  Gregory Zuccaro,et al.  Optical coherence tomography in the gastrointestinal tract. , 2004, Gastrointestinal endoscopy clinics of North America.

[24]  C K Hitzenberger,et al.  Signal and resolution enhancements in dual beam optical coherence tomography of the human eye. , 1998, Journal of biomedical optics.

[25]  T. Desmettre,et al.  Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. , 2000, Survey of ophthalmology.

[26]  M. Rajadhyaksha,et al.  In vivo abnormal keratinization in Darier‐White's disease as viewed by real‐time confocal imaging , 1999, Journal of cutaneous pathology.

[27]  A J Welch,et al.  Penetration depth limits of in vivo confocal reflectance imaging. , 1998, Applied optics.

[28]  J. Fujimoto,et al.  Optical coherence microscopy in scattering media. , 1994, Optics letters.

[29]  David A. Schultz,et al.  Single-target molecule detection with nonbleaching multicolor optical immunolabels. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  B Palcic,et al.  Malignancy associated changes in cervical smears: systematic changes in cytometric features with the grade of dysplasia. , 1995, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[31]  C. Compton,et al.  High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography. , 2000, Gastrointestinal endoscopy.

[32]  Yunjiang Rao,et al.  Synthesized source for white-light sensing systems. , 1993, Optics letters.

[33]  J G Fujimoto,et al.  Correlation of collagen organization with polarization sensitive imaging of in vitro cartilage: implications for osteoarthritis. , 2001, The Journal of rheumatology.

[34]  G. Gelikonov,et al.  In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa. , 1997, Optics express.

[35]  J. Fujimoto,et al.  In vivo endoscopic optical biopsy with optical coherence tomography. , 1997, Science.

[36]  J. Izatt,et al.  Optical Coherence Tomography and Microscopy in Gastrointestinal Tissues , 1996, Advances in Optical Imaging and Photon Migration.

[37]  R. Webb,et al.  Fiber-coupled multiplexed confocal microscope. , 2000, Optics letters.

[38]  T. Wilson,et al.  Fibre-optic based confocal scanning microscopy with semiconductor laser excitation and detection , 1992 .

[39]  G. Gelikonov,et al.  Endoscopic applications of optical coherence tomography. , 1998, Optics express.

[40]  J. V. Bacus,et al.  Properties of Intraepithelial Neoplasia Relevant to Cancer Chemoprevention and to the Development of Surrogate End Points for Clinical Trials , 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[41]  G. Gelikonov,et al.  Optical coherence tomography of the esophagus and proximal stomach in health and disease , 2001, American Journal of Gastroenterology.

[42]  M. Harris,et al.  Fiber-optic laser scanning confocal microscope suitable for fluorescence imaging. , 1994, Applied optics.

[43]  B. Macq,et al.  Morphological feature extraction for the classification of digital images of cancerous tissues , 1996, IEEE Transactions on Biomedical Engineering.

[44]  G Fujimoto James,et al.  Optical Coherence Tomography for Optical Biopsy , 2000 .

[45]  Jennifer K. Barton,et al.  Imaging vascular implants with optical coherence tomography , 2000, Photonics West - Biomedical Optics.

[46]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. , 1999, The Journal of investigative dermatology.

[47]  Joseph A Izatt,et al.  Imaging of the Atrioventricular Node Using Optical Coherence Tomography , 2002, Journal of cardiovascular electrophysiology.

[48]  R Richards-Kortum,et al.  Fiber confocal reflectance microscope (FCRM) for in-vivo imaging. , 2001, Optics express.

[49]  V Westphal,et al.  High-resolution endoscopic imaging of the GI tract: a comparative study of optical coherence tomography versus high-frequency catheter probe EUS. , 2001, Gastrointestinal endoscopy.

[50]  J. Izatt,et al.  Image enhancement in optical coherence tomography using deconvolution , 1997 .

[51]  M M Haglund,et al.  Enhanced optical imaging of human gliomas and tumor margins. , 1996, Neurosurgery.

[52]  Joseph A. Izatt,et al.  In-situ visualization and evaluation of neoplastic lesions of the human gastrointestinal tract using endoscopic optical coherence tomography , 2001, SPIE BiOS.

[53]  Y Zhang,et al.  Resolution improvement in optical coherence tomography by optimal synthesis of light-emitting diodes. , 2001, Optics letters.

[54]  Alexander M. Sergeev,et al.  In-vivo optical coherent tomography of teeth and oral mucosa , 1999, European Conference on Biomedical Optics.

[55]  J. Fujimoto,et al.  Ultrahigh-resolution optical coherence tomography using continuum generation in an air-silica microstructure optical fiber. , 2001, Optics letters.

[56]  Hiroyasu Itoh,et al.  Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase , 2001, Nature.

[57]  R. Lotan,et al.  Autofluorescence Microscopy of Fresh Cervical-Tissue Sections Reveals Alterations in Tissue Biochemistry with Dysplasia¶ , 2001, Photochemistry and photobiology.

[58]  A. Gmitro,et al.  Confocal microscopy through a fiber-optic imaging bundle. , 1993, Optics letters.

[59]  R. Haskell,et al.  Optical coherence microscopy. A technology for rapid, in vivo, non-destructive visualization of plants and plant cells. , 2000, Plant physiology.

[60]  P. Holliger,et al.  Engineering Antibodies for the Clinic , 2004, Cancer and Metastasis Reviews.

[61]  P Corcuff,et al.  In vivo spatio-temporal visualization of the human skin by real-time confocal microscopy. , 1994, Scanning.

[62]  M A Onofre,et al.  Reliability of toluidine blue application in the detection of oral epithelial dysplasia and in situ and invasive squamous cell carcinomas. , 2001, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[63]  R. Anderson,et al.  Confocal laser microscopic imaging of actinic keratoses in vivo: a preliminary report. , 2000, Journal of the American Academy of Dermatology.

[64]  Raghavan Rajagopalan,et al.  Site-specific tumor-targeted fluorescent contrast agents , 2001, European Conference on Biomedical Optics.

[65]  B E Bouma,et al.  Scanning single-mode fiber optic catheter-endoscope for optical coherence tomography: erratum. , 1996, Optics letters.

[66]  M. Bashkansky,et al.  Statistics and reduction of speckle in optical coherence tomography. , 2000, Optics letters.

[67]  M. Rajadhyaksha,et al.  Confocal reflectance imaging of folliculitis in vivo: correlation with routine histology , 1999, Journal of cutaneous pathology.

[68]  G. V. Rosmalen,et al.  Confocal compact scanning optical microscope based on compact disc technology. , 1991, Applied optics.

[69]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[70]  W. Rudolph,et al.  Analysis of heterodyne and confocal microscopy for illumination with broad-bandwidth light , 1996 .

[71]  David A. Jackson,et al.  Three dimensional OCT images from retina and skin. , 2000, Optics express.

[72]  Ruikang K. Wang Resolution improved optical coherence-gated tomography for imaging through biological tissues , 1999 .

[73]  B. Bouma,et al.  Power-efficient nonreciprocal interferometer and linear-scanning fiber-optic catheter for optical coherence tomography. , 1999, Optics letters.

[74]  Michele Follen,et al.  Near real-time confocal microscopy of amelanotic tissue: detection of dysplasia in ex vivo cervical tissue. , 2002, Academic radiology.

[75]  J Mertz,et al.  Combined scanning optical coherence and two-photon-excited fluorescence microscopy. , 1999, Optics letters.

[76]  J. Fujimoto,et al.  Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus. , 2000, Endoscopy.

[77]  S. Achilefu,et al.  Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. , 2001, Journal of biomedical optics.

[78]  M Rajadhyaksha,et al.  Allergic contact dermatitis: correlation of in vivo confocal imaging to routine histology. , 1999, Journal of the American Academy of Dermatology.

[79]  Colin J. R. Sheppard,et al.  Fluorescent image formation in the fibre-optical confocal scanning microscope , 1992 .

[80]  S. Owens,et al.  Indocyanine green angiography. , 1996, The British journal of ophthalmology.

[81]  R. Richards-Kortum,et al.  In vivo optical coherence tomography measurements in the cervix using a fiber optic probe , 1998, Technical Digest. Summaries of Papers Presented at the Conference on Lasers and Electro-Optics. Conference Edition. 1998 Technical Digest Series, Vol.6 (IEEE Cat. No.98CH36178).

[82]  M. Rajadhyaksha,et al.  Confocal imaging of sebaceous gland hyperplasia in vivo to assess efficacy and mechanism of pulsed dye laser treatment , 1999, Lasers in surgery and medicine.

[83]  R Richards-Kortum,et al.  Near real time confocal microscopy of amelanotic tissue: dynamics of aceto-whitening enable nuclear segmentation. , 2000, Optics express.

[84]  R Richards-Kortum,et al.  Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved. , 2002, Journal of microscopy.

[85]  Joseph M. Schmitt,et al.  An optical coherence microscope with enhanced resolving power , 1997 .

[86]  R. Webb,et al.  Video-rate confocal scanning laser microscope for imaging human tissues in vivo. , 1999, Applied optics.

[87]  A. Dunn,et al.  Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents and limits of contrast. , 1998, Journal of biomedical optics.

[88]  J. Nelson,et al.  Imaging blood flow in human port-wine stain in situ and in real time using optical Doppler tomography. , 2001, Archives of dermatology.

[89]  V. Steele,et al.  Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy. , 1992, Cancer research.

[90]  J. Schmitt,et al.  Confocal microscopy in turbid media. , 1994, Journal of the Optical Society of America. A, Optics, image science, and vision.

[91]  M. Horisberger,et al.  Colloidal gold : a cytochemical marker for light and fluorescent microscopy and for transmission and scanning electron microscopy. , 1981, Scanning electron microscopy.

[92]  K. Sokolov,et al.  Surface-enhanced Raman spectroscopy and its biomedical applications , 1993 .

[93]  David J. Webb,et al.  Transversal and longitudinal images from the retina of the living eye using low coherence reflectometry. , 1998, Journal of biomedical optics.

[94]  Thomas E. Milner,et al.  Optical Doppler Tomography , 1999, Definitions.

[95]  A F Gmitro,et al.  Rapid observation of unfixed, unstained human skin biopsy specimens with confocal microscopy and visualization. , 1997, Journal of biomedical optics.

[96]  P. Prasad,et al.  Confocal enhanced optical coherence tomography for nondestructive evaluation of paints and coatings. , 1999, Optics letters.

[97]  D. Scheinberg,et al.  Monoclonal antibody therapy of cancer. , 1990, Cancer chemotherapy and biological response modifiers.

[98]  R. Lotan,et al.  Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid. , 2000, American journal of obstetrics and gynecology.

[99]  Woo Kyung Moon,et al.  A Receptor‐Targeted Near‐Infrared Fluorescence Probe for In Vivo Tumor Imaging , 2002, Chembiochem : a European journal of chemical biology.

[100]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[101]  C. Luchini,et al.  [High speed]. , 1969, Revista De La Escuela De Odontologia, Universidad Nacional De Tucuman, Facultad De Medicina.

[102]  R. J. Joseph,et al.  Advances in Computational Electrodynamics: The Finite - Di erence Time - Domain Method , 1998 .

[103]  Paul Mulvaney,et al.  Surface Plasmon Spectroscopy of Nanosized Metal Particles , 1996 .

[104]  M. Rajadhyaksha,et al.  Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo. , 2001, Journal of the American Academy of Dermatology.

[105]  G. Ripandelli,et al.  Optical coherence tomography. , 1998, Seminars in ophthalmology.

[106]  W. Tan,et al.  Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers. , 2001, Analytical chemistry.

[107]  Calum MacAulay,et al.  DMD-enabled confocal microendoscopy , 2001, SPIE BiOS.

[108]  J. Storhoff,et al.  Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. , 1997, Science.

[109]  David A. Jackson,et al.  En-face coherence imaging using galvanometer scanner modulation. , 1998, Optics letters.

[110]  R. Webb,et al.  Spectrally encoded confocal microscopy. , 1998, Optics letters.

[111]  R. Richards-Kortum,et al.  Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture. , 2003, Journal of biomedical optics.

[112]  G. Carpenter,et al.  Receptors for epidermal growth factor and other polypeptide mitogens. , 1987, Annual review of biochemistry.

[113]  E. Sevick-Muraca,et al.  Quantitative optical spectroscopy for tissue diagnosis. , 1996, Annual review of physical chemistry.

[114]  M Rajadhyaksha,et al.  Noninvasive Imaging of Human Oral Mucosa in Vivo by Confocal Reflectance Microscopy , 1999, The Laryngoscope.

[115]  P. Corcuff,et al.  In vivo confocal microscopy of human skin: a new design for cosmetology and dermatology. , 2006, Scanning.

[116]  Gordon S. Kino,et al.  Scanned optical fiber confocal microscope , 1994, Electronic Imaging.

[117]  Andrew M. Rollins,et al.  High-speed full-field optical coherence microscopy , 1999, Photonics West - Biomedical Optics.

[118]  M. Rajadhyaksha,et al.  Characterization of psoriasis in vivo by reflectance confocal microscopy. , 1999, Journal of medicine.

[119]  Katharine Grieve,et al.  Full-field optical coherence microscopy , 2004, Advanced Laser Technologies.

[120]  Joseph M. Schmitt,et al.  Optical coherence tomography (OCT): a review , 1999 .

[121]  M. K Rollert,et al.  Sensitivity and specificity of orascan toluidine blue mouthrinse in the detection of oral cancer and precancer , 1997 .

[122]  Jennifer Kehlet Barton,et al.  Use of microbubbles as an optical coherence tomography contrast agent. , 2002, Academic radiology.

[123]  W. D. Geoghegan,et al.  Adsorption of horseradish peroxidase, ovomucoid and anti-immunoglobulin to colloidal gold for the indirect detection of concanavalin A, wheat germ agglutinin and goat anti-human immunoglobulin G on cell surfaces at the electron microscopic level: a new method, theory and application. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[124]  G. Rustin,et al.  Role of tumour markers in monitoring epithelial ovarian cancer , 2000, British Journal of Cancer.

[125]  U Seitz,et al.  In vivo endoscopic optical coherence tomography of the human gastrointestinal tract--toward optical biopsy. , 2000, Endoscopy.

[126]  M D Duncan,et al.  Subsurface defect detection in ceramics by high-speed high-resolution optical coherent tomography. , 1997, Optics letters.

[127]  W. Semmler,et al.  Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands , 2001, Nature Biotechnology.

[128]  I. Ramzy Essentials of Gynecologic and Obstetric Pathology , 1982 .

[129]  C. Contag,et al.  Advance in contrast agents, reporters, and detection. , 2001, Journal of biomedical optics.

[130]  J. Izatt,et al.  Real-time in vivo imaging of human gastrointestinal ultrastructure by use of endoscopic optical coherence tomography with a novel efficient interferometer design. , 1999, Optics letters.

[131]  H. Honda,et al.  Detection of human gastric cancer in resected specimens using a novel infrared fluorescent anti-human carcinoembryonic antigen antibody with an infrared fluorescence endoscope in vitro. , 2001, Endoscopy.

[132]  S. L. Westcott,et al.  Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery. , 2000, Journal of biomedical materials research.

[133]  G. Kino,et al.  Silicon-micromachined scanning confocal optical microscope , 1998 .