Abstract

We demonstrate vertical cross-sectional (XZ-plane) images of near-infrared (NIR) fluorescence with a handheld dual axes confocal endomicroscope that reveals specific binding of a Cy5.5-labeled peptide to pre-malignant colonic mucosa. This view is perpendicular to the tissue surface, and is similar to that used by pathologists. The scan head is 10 mm in outer diameter (OD), and integrates a one dimensional (1-D) microelectromechanical systems (MEMS) X-axis scanner and a bulky lead zirconate titanate (PZT) based Z-axis actuator. The microscope images in a raster-scanning pattern with a ±6 degrees (mechanical) scan angle at ~3 kHz in the X-axis (fast) and up to 10 Hz (0–400 μm) in the Z-axis (slow). Vertical cross-sectional fluorescence images are collected with a transverse and axial resolution of 4 and 5 μm, respectively, over a field-of-view of 800 μm (width) × 400 μm (depth). NIR vertical cross-sectional fluorescence images of fresh mouse colonic mucosa demonstrate histology-like imaging performance with this miniature instrument.

© 2013 OSA

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  1. T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
    [CrossRef] [PubMed]
  2. R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
    [CrossRef] [PubMed]
  3. H. J. Shin, M. C. Pierce, D. Lee, H. Ra, O. Solgaard, and R. Richards-Kortum, “Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens,” Opt. Express15(15), 9113–9122 (2007).
    [CrossRef] [PubMed]
  4. C. L. Arrasmith, D. L. Dickensheets, and A. Mahadevan-Jansen, “MEMS-based handheld confocal microscope for in-vivo skin imaging,” Opt. Express18(4), 3805–3819 (2010).
    [CrossRef] [PubMed]
  5. J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
    [CrossRef] [PubMed]
  6. 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,” Science254(5035), 1178–1181 (1991).
    [CrossRef] [PubMed]
  7. K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
    [CrossRef] [PubMed]
  8. N. Callamaras and I. R. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium26(6), 271–279 (1999).
    [CrossRef] [PubMed]
  9. W. Göbel, B. M. Kampa, and F. Helmchen, “Imaging cellular network dynamics in three dimensions using fast 3D laser scanning,” Nat. Methods4(1), 73–79 (2007).
    [CrossRef] [PubMed]
  10. H. Mansoor, H. Zeng, K. Chen, Y. Yu, J. Zhao, and M. Chiao, “Vertical optical sectioning using a magnetically driven confocal microscanner aimed for in vivo clinical imaging,” Opt. Express19(25), 25161–25172 (2011).
    [CrossRef] [PubMed]
  11. K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
    [CrossRef] [PubMed]
  12. T. D. Wang, M. J. Mandella, C. H. Contag, and G. S. Kino, “Dual-axis confocal microscope for high-resolution in vivo imaging,” Opt. Lett.28(6), 414–416 (2003).
    [CrossRef] [PubMed]
  13. J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
    [CrossRef] [PubMed]
  14. W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
    [CrossRef] [PubMed]
  15. L. K. Wong, M. J. Mandella, G. S. Kino, and T. D. Wang, “Improved rejection of multiply scattered photons in confocal microscopy using dual-axes architecture,” Opt. Lett.32(12), 1674–1676 (2007).
    [CrossRef] [PubMed]
  16. P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
    [CrossRef] [PubMed]
  17. S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
    [CrossRef] [PubMed]
  18. K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
    [CrossRef]
  19. H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
    [CrossRef]
  20. Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
    [CrossRef]

2012

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

2011

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

H. Mansoor, H. Zeng, K. Chen, Y. Yu, J. Zhao, and M. Chiao, “Vertical optical sectioning using a magnetically driven confocal microscanner aimed for in vivo clinical imaging,” Opt. Express19(25), 25161–25172 (2011).
[CrossRef] [PubMed]

2010

C. L. Arrasmith, D. L. Dickensheets, and A. Mahadevan-Jansen, “MEMS-based handheld confocal microscope for in-vivo skin imaging,” Opt. Express18(4), 3805–3819 (2010).
[CrossRef] [PubMed]

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

2008

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

2007

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

W. Göbel, B. M. Kampa, and F. Helmchen, “Imaging cellular network dynamics in three dimensions using fast 3D laser scanning,” Nat. Methods4(1), 73–79 (2007).
[CrossRef] [PubMed]

L. K. Wong, M. J. Mandella, G. S. Kino, and T. D. Wang, “Improved rejection of multiply scattered photons in confocal microscopy using dual-axes architecture,” Opt. Lett.32(12), 1674–1676 (2007).
[CrossRef] [PubMed]

H. J. Shin, M. C. Pierce, D. Lee, H. Ra, O. Solgaard, and R. Richards-Kortum, “Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens,” Opt. Express15(15), 9113–9122 (2007).
[CrossRef] [PubMed]

2004

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

2003

2001

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

1999

N. Callamaras and I. R. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium26(6), 271–279 (1999).
[CrossRef] [PubMed]

1998

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

1991

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Adams, S. G.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Arrasmith, C. L.

Burg, J.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Burns, L. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Callamaras, N.

N. Callamaras and I. R. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium26(6), 271–279 (1999).
[CrossRef] [PubMed]

Chang, W.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, K.

Chiao, M.

Choi, M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Cocker, E. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Contag, C. H.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

T. D. Wang, M. J. Mandella, C. H. Contag, and G. S. Kino, “Dual-axis confocal microscope for high-resolution in vivo imaging,” Opt. Lett.28(6), 414–416 (2003).
[CrossRef] [PubMed]

Crawford, J. M.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Delaney, P.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Dickensheets, D. L.

Du, C. B.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

Dürr, P.

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

Enders, M.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Flotte, T.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Friedland, S.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Fujimoto, J. G.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Galle, P. R.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Gamal, A. E.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Gaustad, A.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

Ghosh, K. K.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Gnaendiger, J.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Göbel, W.

W. Göbel, B. M. Kampa, and F. Helmchen, “Imaging cellular network dynamics in three dimensions using fast 3D laser scanning,” Nat. Methods4(1), 73–79 (2007).
[CrossRef] [PubMed]

Gregory, K.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hardy, J.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

Hartwell, P. G.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Hee, M. R.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Helmchen, F.

W. Göbel, B. M. Kampa, and F. Helmchen, “Imaging cellular network dynamics in three dimensions using fast 3D laser scanning,” Nat. Methods4(1), 73–79 (2007).
[CrossRef] [PubMed]

Hsiung, P. L.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Huang, D.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Ibrahim, S. F.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Janell, D.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Joshi, B. P.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

Jung, K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Kampa, B. M.

W. Göbel, B. M. Kampa, and F. Helmchen, “Imaging cellular network dynamics in three dimensions using fast 3D laser scanning,” Nat. Methods4(1), 73–79 (2007).
[CrossRef] [PubMed]

Khoudeir, L.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Kiesslich, R.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Kim, J. K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Kim, P.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Kim, S.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Kino, G. S.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

L. K. Wong, M. J. Mandella, G. S. Kino, and T. D. Wang, “Improved rejection of multiply scattered photons in confocal microscopy using dual-axes architecture,” Opt. Lett.32(12), 1674–1676 (2007).
[CrossRef] [PubMed]

T. D. Wang, M. J. Mandella, C. H. Contag, and G. S. Kino, “Dual-axis confocal microscope for high-resolution in vivo imaging,” Opt. Lett.28(6), 414–416 (2003).
[CrossRef] [PubMed]

Kück, H.

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

Kunze, D.

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

Lakner, H.

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

Lee, C. M.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

Lee, D.

Lee, K. S.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Lee, W. M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Lin, C. P.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Lin, X.

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Liu, J. T. C.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Loewke, K.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

Lowe, A. W.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

MacDonald, N. C.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Mahadevan-Jansen, A.

Mandella, M. J.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

L. K. Wong, M. J. Mandella, G. S. Kino, and T. D. Wang, “Improved rejection of multiply scattered photons in confocal microscopy using dual-axes architecture,” Opt. Lett.32(12), 1674–1676 (2007).
[CrossRef] [PubMed]

T. D. Wang, M. J. Mandella, C. H. Contag, and G. S. Kino, “Dual-axis confocal microscope for high-resolution in vivo imaging,” Opt. Lett.28(6), 414–416 (2003).
[CrossRef] [PubMed]

Mansoor, H.

McLaren, W.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Meemon, N.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Miller, S. A.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Miller, S. J.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

Nafe, B.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Neurath, M. F.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Nimmerjahn, A.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Oldham, K.

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Parker, I. R.

N. Callamaras and I. R. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium26(6), 271–279 (1999).
[CrossRef] [PubMed]

Pierce, M. C.

Piyawattanametha, W.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

Polcawich, R.

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Polglase, A.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Puliafito, C. A.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Pulskamp, J.

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Qiu, Z.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Ra, H.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

H. J. Shin, M. C. Pierce, D. Lee, H. Ra, O. Solgaard, and R. Richards-Kortum, “Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens,” Opt. Express15(15), 9113–9122 (2007).
[CrossRef] [PubMed]

Rhee, C. H.

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

Richards-Kortum, R.

Rolland, J. P.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Sahbaie, P.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Schenk, H.

H. Schenk, P. Dürr, D. Kunze, H. Lakner, and H. Kück, “A resonantly excited 2D-micro-scanning-mirror with large deflection,” Sens. Actuators A Phys.89(1–2), 104–111 (2001).
[CrossRef]

Schnitzer, M. J.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Schuman, J. S.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Seibel, E. J.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

Shin, H. J.

Soetikno, R.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Solgaard, O.

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

H. J. Shin, M. C. Pierce, D. Lee, H. Ra, O. Solgaard, and R. Richards-Kortum, “Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens,” Opt. Express15(15), 9113–9122 (2007).
[CrossRef] [PubMed]

Stinson, W. G.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Strogatz, S. H.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Swanson, E. A.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Thomas, S.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Turner, K. L.

K. L. Turner, S. A. Miller, P. G. Hartwell, N. C. MacDonald, S. H. Strogatz, and S. G. Adams, “Five parametric resonances in a micro-electro-mechanical system,” Nature396(6707), 149–152 (1998).
[CrossRef]

Vieth, M.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

Wang, T. D.

S. J. Miller, C. M. Lee, B. P. Joshi, A. Gaustad, E. J. Seibel, and T. D. Wang, “Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy,” J. Biomed. Opt.17(2), 021103 (2012).
[CrossRef] [PubMed]

W. Piyawattanametha, H. Ra, Z. Qiu, S. Friedland, J. T. C. Liu, K. Loewke, G. S. Kino, O. Solgaard, T. D. Wang, M. J. Mandella, and C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt.17(2), 021102 (2012).
[CrossRef] [PubMed]

Z. Qiu, J. Pulskamp, X. Lin, C. H. Rhee, T. D. Wang, R. Polcawich, and K. Oldham, “Large displacement vertical translational actuator based on piezoelectric thin films,” J. Micromech. Microeng.20(7), 075016 (2010).
[CrossRef]

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

J. T. C. Liu, M. J. Mandella, J. M. Crawford, C. H. Contag, T. D. Wang, and G. S. Kino, “Efficient rejection of scattered light enables deep optical sectioning in turbid media with low-numerical-aperture optics in a dual-axis confocal architecture,” J. Biomed. Opt.13(3), 034020 (2008).
[CrossRef] [PubMed]

L. K. Wong, M. J. Mandella, G. S. Kino, and T. D. Wang, “Improved rejection of multiply scattered photons in confocal microscopy using dual-axes architecture,” Opt. Lett.32(12), 1674–1676 (2007).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

T. D. Wang, M. J. Mandella, C. H. Contag, and G. S. Kino, “Dual-axis confocal microscope for high-resolution in vivo imaging,” Opt. Lett.28(6), 414–416 (2003).
[CrossRef] [PubMed]

Wong, L. K.

Wu, A. P.

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med.14(4), 454–458 (2008).
[CrossRef] [PubMed]

Yu, Y.

Yun, S. H.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc.7(8), 1456–1469 (2012).
[CrossRef] [PubMed]

Zeng, H.

Zhao, H.

K. S. Lee, H. Zhao, S. F. Ibrahim, N. Meemon, L. Khoudeir, and J. P. Rolland, “Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy,” J. Biomed. Opt.17(12), 126006 (2012).
[CrossRef] [PubMed]

Zhao, J.

Ziv, Y.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods8(10), 871–878 (2011).
[CrossRef] [PubMed]

Cell Calcium

N. Callamaras and I. R. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium26(6), 271–279 (1999).
[CrossRef] [PubMed]

Clin. Gastroenterol. Hepatol.

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. C. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol.5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Gastroenterology

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology127(3), 706–713 (2004).
[CrossRef] [PubMed]

J. Biomed. Opt.

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Figures (5)

Fig. 1
Fig. 1

Endomicroscope schematic. (a) Cross-sectional view of dual axes architecture shows ray-trace simulation in ZEMAX for achieving 800 μm (width) × 400 μm (depth) images. (b) Optical circuit design for vertical cross-sectional imaging with fiber-coupled achromatic collimators. Components: (1) aluminum coated parabolic mirror with solid immersion lens (SIL) in center; (2) MEMS mirror with PCB holder; (3) prism with holder; (4) achromatic doublet lens based collimator; (5) single mode fiber; (6) achromatic lens; (7) illumination (red) and collection beam (gray).

Fig. 2
Fig. 2

MEMS 1-D (X-axis) resonant scanner. (a) Stereomicroscope image of mirror. Red spot represents reflected He-Ne (633nm) laser beam from gold coated reflective surface. Components: (1) hinge; (2) electric isolation trench; (3) link-arm struts; (4) sensor pad; (5) four weight-reducing holes; (6) electrostatic comb-drive actuators; (7) electric Au/Cr pad; (8) Au/Cr coated reflective mirror surface. (b) Frequency response of MEMS scanner is shown from sweeping the frequency with 10 Hz step size, forward (blue) and backward (red) with 40 V and 50% duty cycle. (c) Schematic of cross-sectional view of the MEMS 1-D scanner design for a 3 × 2 mm2 SOI device with pattern gold coating using DRIE on the top and bottom layers.

Fig. 3
Fig. 3

Schematic of handheld dual axes endomicroscope packaging. (a) Cross-sectional view of system packaging without protection shell shows inner integrated XZ-plane 2D scan engine for vertical cross-sectional imaging (inset: handheld prototype); (b) Magnified view of XZ-plane 2D scan engine design. Components: (1) Z-axis piezo actuator; (2) “T-shape” cantilever on the tip of PZT actuator; (3) parabolic mirror and its holder; (4) prism holder clamp; (5) tube jacket; (6) collimator housing tube; (7) PZT actuator holder; (8) Au bonding wire for electricity connection.

Fig. 4
Fig. 4

Instrument resolution. (a) En-face (XY-plane) reflectance image of a standard target shows lateral resolution of 4 μm, FOV 400 × 400 µm2, scale bar 50 μm. (b) Axial scan from a reflective target shows FWHM of 5 μm at depth of 250 μm in a scattering-free deionized-water film.

Fig. 5
Fig. 5

Vertical cross-sectional image of colonic dysplasia. (a) Chemical structure of LTTHYKL peptide (black) with GGGSK linker (blue) and Cy5.5 fluorophore (red). (b) NIR fluorescence image from CPC;Apc mouse colon ex vivo shows vertically oriented dysplastic crypts. (800 × 400 μm2 FOV) (c) The border between normal colonic mucosa and dysplasia shows increased contrast from specific binding of the LTT*-Cy5.5 peptide. (800 × 400 μm2 FOV) (d) Corresponding histology (H&E), scale bar 200 µm.

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