Abstract

We report a fully packaged and compact forward viewing endomicroscope by using a resonant fiber scanner with two dimensional Lissajous trajectories. The fiber scanner comprises a single mode fiber with additional microstructures mounted inside a piezoelectric tube with quartered electrodes. The mechanical cross-coupling between the transverse axes of a resonant fiber with a circular cross-section was completely eliminated by asymmetrically modulating the stiffness of the fiber cantilever with silicon microstructures and an off-set fiber fragment. The Lissajous fiber scanner was fully packaged as endomicroscopic catheter passing through the accessory channel of a clinical endoscope and combined with spectral domain optical coherence tomography (SD-OCT). Ex-vivo 3D OCT images were successfully reconstructed along Lissajous trajectory. The preview imaging capability of the Lissajous scanning enables rapid 3D imaging with high temporal resolution. This endoscopic catheter provides many opportunities for on-demand and non-invasive optical biopsy inside a gastrointestinal endoscope.

© 2014 Optical Society of America

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2013 (1)

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
[CrossRef] [PubMed]

2012 (7)

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, 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.-C. Park, C. Song, M. Kang, Y. Jeong, K.-H. Jeong, “Forward imaging OCT endoscopic catheter based on MEMS lens scanning,” Opt. Lett. 37(13), 2673–2675 (2012).
[CrossRef] [PubMed]

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
[CrossRef] [PubMed]

W. Liang, K. Murari, Y. Zhang, Y. Chen, M.-J. Li, X. Li, “Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy,” J. Biomed. Opt. 17(2), 021108 (2012).
[CrossRef] [PubMed]

T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
[CrossRef] [PubMed]

2011 (2)

C. L. Hoy, N. J. Durr, A. Ben-Yakar, “Fast-updating and nonrepeating Lissajous image reconstruction method for capturing increased dynamic information,” Appl. Opt. 50(16), 2376–2382 (2011).
[CrossRef] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[CrossRef] [PubMed]

2010 (4)

2009 (1)

2008 (2)

2007 (4)

2006 (3)

2005 (1)

2004 (3)

2003 (1)

2001 (2)

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A Miniature Head-Mounted Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

D. Provenzale, J. Onken, “Surveillance issues in inflammatory bowel disease: ulcerative colitis,” J. Clin. Gastroenterol. 32(2), 99–105 (2001).
[CrossRef] [PubMed]

2000 (1)

B. J. Reid, P. L. Blount, Z. Feng, D. S. Levine, “Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia,” Am. J. Gastroenterol. 95(11), 3089–3096 (2000).
[CrossRef] [PubMed]

1993 (1)

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

1991 (1)

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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1988 (1)

B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
[PubMed]

Adler, D. C.

D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, J. G. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photonics 1(12), 709–716 (2007).
[CrossRef]

Aguirre, A. D.

Ahn, Y.-C.

Akins, M. L.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Anderson, E. P.

Bancu, M. G.

Barretto, R. P. J.

Ben-Yakar, A.

Bernstein, J. J.

Blount, P. L.

B. J. Reid, P. L. Blount, Z. Feng, D. S. Levine, “Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia,” Am. J. Gastroenterol. 95(11), 3089–3096 (2000).
[CrossRef] [PubMed]

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

Bouma, B. E.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
[CrossRef] [PubMed]

K. H. Kim, B. H. Park, G. N. Maguluri, T. W. Lee, F. J. Rogomentich, M. G. Bancu, B. E. Bouma, J. F. de Boer, J. J. Bernstein, “Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography,” Opt. Express 15(26), 18130–18140 (2007).
[CrossRef] [PubMed]

Brenner, M.

Brown, C. M.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[CrossRef] [PubMed]

Cai, X.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Carruth, R. W.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
[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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, M.

Chen, R.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Chen, Y.

Chen, Z.

Cobb, M. J.

Cocker, E. D.

Connolly, J.

D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, J. G. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photonics 1(12), 709–716 (2007).
[CrossRef]

Conry, M.

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, 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, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
[CrossRef] [PubMed]

de Boer, J. F.

DenBesten, L.

B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
[PubMed]

Denk, W.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A Miniature Head-Mounted Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Ding, Z.

Durr, N. J.

El Rifai, O. M.

O. M. El Rifai, K. Youcef-Toumi, “Coupling in piezoelectric tube scanners used in scanning probe microscopes,” in Proceedings of the 2001 American Control Conference. (Cat. No.01CH37148) (IEEE, 2001), 5, 3251–3255.
[CrossRef]

Engelbrecht, C. J.

Fan, L.

Favazza, C.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Fedder, G. K.

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A Miniature Head-Mounted Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Feng, Z.

B. J. Reid, P. L. Blount, Z. Feng, D. S. Levine, “Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia,” Am. J. Gastroenterol. 95(11), 3089–3096 (2000).
[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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Flusberg, B. A.

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, 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]

Fujimoto, J. G.

D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, J. G. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photonics 1(12), 709–716 (2007).
[CrossRef]

A. D. Aguirre, P. R. Hertz, Y. Chen, J. G. Fujimoto, W. Piyawattanametha, L. Fan, M. C. Wu, “Two-axis MEMS Scanning Catheter for Ultrahigh Resolution Three-dimensional and En Face Imaging,” Opt. Express 15(5), 2445–2453 (2007).
[CrossRef] [PubMed]

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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gallagher, K. A.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
[CrossRef] [PubMed]

Gora, M. J.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
[CrossRef] [PubMed]

Gregory, K.

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J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
[PubMed]

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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A Miniature Head-Mounted Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
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Hoy, C. L.

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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, J. G. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photonics 1(12), 709–716 (2007).
[CrossRef]

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Jeong, K.-H.

Jeong, Y.

Johnston, R. S.

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Jung, W.

Kang, M.

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T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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Kimmey, M. B.

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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, 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, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
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Lee, D.

Lee, S.-W.

Lee, T. W.

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B. J. Reid, P. L. Blount, Z. Feng, D. S. Levine, “Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia,” Am. J. Gastroenterol. 95(11), 3089–3096 (2000).
[CrossRef] [PubMed]

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

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B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
[PubMed]

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J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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Liang, W.

W. Liang, K. Murari, Y. Zhang, Y. Chen, M.-J. Li, X. Li, “Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy,” J. Biomed. Opt. 17(2), 021108 (2012).
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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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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, 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, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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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, C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
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J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
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T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
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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, C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
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J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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Mukai, D. S.

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Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
[CrossRef] [PubMed]

W. Liang, K. Murari, Y. Zhang, Y. Chen, M.-J. Li, X. Li, “Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy,” J. Biomed. Opt. 17(2), 021108 (2012).
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Nishioka, N. S.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
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Pantazi, A.

T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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Park, H.-C.

Pavlova, I.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
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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, 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, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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A. D. Aguirre, P. R. Hertz, Y. Chen, J. G. Fujimoto, W. Piyawattanametha, L. Fan, M. C. Wu, “Two-axis MEMS Scanning Catheter for Ultrahigh Resolution Three-dimensional and En Face Imaging,” Opt. Express 15(5), 2445–2453 (2007).
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W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, M. J. Schnitzer, “Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror,” Opt. Lett. 31(13), 2018–2020 (2006).
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D. Provenzale, J. Onken, “Surveillance issues in inflammatory bowel disease: ulcerative colitis,” J. Clin. Gastroenterol. 32(2), 99–105 (2001).
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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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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, 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]

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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, C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
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J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, M. J. Schnitzer, “Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror,” Opt. Lett. 31(13), 2018–2020 (2006).
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D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

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B. J. Reid, P. L. Blount, Z. Feng, D. S. Levine, “Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia,” Am. J. Gastroenterol. 95(11), 3089–3096 (2000).
[CrossRef] [PubMed]

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
[PubMed]

B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
[PubMed]

Rivera, D. R.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
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Rogomentich, F. J.

Rosenberg, M.

M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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B. J. Reid, W. M. Weinstein, K. J. Lewin, R. C. Haggitt, G. VanDeventer, L. DenBesten, C. E. Rubin, “Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett’s esophagus without grossly recognizable neoplastic lesions,” Gastroenterology 94(1), 81–90 (1988).
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Rusch, V. W.

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
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M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, J. G. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photonics 1(12), 709–716 (2007).
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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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Sepehr, A.

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J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
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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, C. H. Contag, “In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract,” J. Biomed. Opt. 17(2), 021102 (2012).
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J. T. C. Liu, M. J. Mandella, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
[CrossRef] [PubMed]

W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, M. J. Schnitzer, “Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror,” Opt. Lett. 31(13), 2018–2020 (2006).
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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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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, J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A Miniature Head-Mounted Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
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M. J. Gora, J. S. Sauk, R. W. Carruth, K. A. Gallagher, M. J. Suter, N. S. Nishioka, L. E. Kava, M. Rosenberg, B. E. Bouma, G. J. Tearney, “Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure,” Nat. Med. 19(2), 238–240 (2013).
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T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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Wang, F.

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Xu, C.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[CrossRef] [PubMed]

Yang, C.

Yang, J.-M.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Yao, J.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
[CrossRef] [PubMed]

Yaqoob, Z.

Youcef-Toumi, K.

O. M. El Rifai, K. Youcef-Toumi, “Coupling in piezoelectric tube scanners used in scanning probe microscopes,” in Proceedings of the 2001 American Control Conference. (Cat. No.01CH37148) (IEEE, 2001), 5, 3251–3255.
[CrossRef]

Zhang, Y.

W. Liang, K. Murari, Y. Zhang, Y. Chen, M.-J. Li, X. Li, “Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy,” J. Biomed. Opt. 17(2), 021108 (2012).
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J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li, X. Li, “Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging,” Opt. Lett. 37(3), 362–364 (2012).
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Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Zhou, Q.

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
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Appl. Opt. (2)

Clin. Gastroenterol. Hepatol. (1)

T. D. Wang, J. Van Dam, “Optical biopsy: A new frontier in endoscopic detection and diagnosis,” Clin. Gastroenterol. Hepatol. 2(9), 744–753 (2004).
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Gastroenterology (2)

D. S. Levine, R. C. Haggitt, P. L. Blount, P. S. Rabinovitch, V. W. Rusch, B. J. Reid, “An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus,” Gastroenterology 105(1), 40–50 (1993).
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[PubMed]

J. Biomed. Opt. (3)

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, 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, N. O. Loewke, H. Haeberle, H. Ra, W. Piyawattanametha, O. Solgaard, G. S. Kino, C. H. Contag, “Micromirror-scanned dual-axis confocal microscope utilizing a gradient-index relay lens for image guidance during brain surgery,” J. Biomed. Opt. 15(2), 026029 (2010).
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W. Liang, K. Murari, Y. Zhang, Y. Chen, M.-J. Li, X. Li, “Increased illumination uniformity and reduced photodamage offered by the Lissajous scanning in fiber-optic two-photon endomicroscopy,” J. Biomed. Opt. 17(2), 021108 (2012).
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T. Tuma, J. Lygeros, V. Kartik, A. Sebastian, A. Pantazi, “High-speed multiresolution scanning probe microscopy based on Lissajous scan trajectories,” Nanotechnology 23(18), 185501 (2012).
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Nat. Med. (2)

J.-M. Yang, C. Favazza, R. Chen, J. Yao, X. Cai, K. Maslov, Q. Zhou, K. K. Shung, L. V. Wang, “Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo,” Nat. Med. 18(8), 1297–1302 (2012).
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Nat. Photonics (1)

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Neuron (1)

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Opt. Express (7)

T. Wu, Z. Ding, K. Wang, M. Chen, C. Wang, “Two-dimensional scanning realized by an asymmetry fiber cantilever driven by single piezo bender actuator for optical coherence tomography,” Opt. Express 17(16), 13819–13829 (2009).
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C. J. Engelbrecht, R. S. Johnston, E. J. Seibel, F. Helmchen, “Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo,” Opt. Express 16(8), 5556–5564 (2008).
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Opt. Lett. (10)

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Proc. Natl. Acad. Sci. U.S.A. (2)

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[CrossRef] [PubMed]

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M.-J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
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[CrossRef]

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Figures (4)

Fig. 1
Fig. 1

(a) Schematic illustration of a Lissajous fiber scanner mounted inside a quardrapole piezoelectic tube with micromachined silicon structures. (b) Time-lapse sequence of Lissajous scanning patterns. The mechanical stiffness of a scanning fiber with a circular cross-section is tuned by mounting additional microstuctures along the off-axis, which results in Lissajous scan trajectories due to the separation of resonant frequencies along transverse axes. The scan density during Lissajous scanning continuously increases and covers the entire field of view.

Fig. 2
Fig. 2

Lissajous fiber scanner; (a) Microfabrication method for supporting silicon structures. The silicon structures were fabricated by using conventional DRIE process with 6 inch silicon wafer. (b) Optical images of a micromachined silicon substrate; silicon microstructures can be arbitrarily shaped by using MEMS microfabrication techniques. (c) An optical image of a single silicon microstructure; the fiber groove was defined on a silicon structure to assist the precise assembly. The individual silicon structures were tethered on a silicon wafer and separated by breaking them with Joule heating. (d) An optical image of fully micro-assembled Lissajous fiber scanner. A 20 mm long fiber cantilever with additional supporting structures was mounted on a PZT tube.

Fig. 3
Fig. 3

(a)-(c) Optical images of resonant scanning fiber cantilevers and biaxial scan patterns; (a) 20 mm long bare fiber cantilever, (b) fiber cantilever with three additional masses, (c) fiber cantilever with additional supporting structures. Bottom three images are corresponds to the 1D resonant scan patterns of x-axis (left), y-axis (center), and 2D scan pattern (right), respectively. Ellipsoidal scan patterns were observed due to the mechanical cross-coupling (a) and became more significant due to the high resonance gain induced by additional mass (b). The cross-coupling phenomena were completely eliminated with additional supporting structure, which enables to obtain clear line scan patterns and Lissajous scanning (c). (d)-(e) Frequency response of resonant fiber scanner. A 20 mm long fiber cantilever with a circular cross-section originally has the resonance at 269 Hz for both x and y directions. With three additional silicon masses at the distal end of a fiber, the resonant frequency was decreased to 85 Hz, while the mechanical Q-factor increases. The resonance bandwidth, which a resonance gain reduced to 1/15, was 10 Hz (indicated with red arrow). (e) Frequency response of the resonant fiber scanner with additional supporting structure. The supporting structure distinguishes the resonance frequencies of both axes; 86 Hz for x-axis, and 97 Hz for y-axis, respectively. Scanning amplitude of 732 µm and 591.7 µm for x and y axes, respectively, were obtained with peak-to-peak 40 Vac applied voltages. (e) A second-order regression model for the resonant frequency difference between two orthogonal axes of the 20 mm long fiber cantilever, with respect to the position of additional structures, L1, and length, L2. The mechanical dimensions of the supporting structure were carefully selected regarding on the numerical analysis within above horizontal red plane area (df >10 Hz), for sufficiently separating the resonant frequencies of orthogonal axes to eliminate the mechanical cross-coupling. (f) The resonant frequency of each axis under a constant L1 of 3.5 mm depending on L2. The stiffness of a fiber fragment decreases as the fragment length L2 increases over 10 mm.

Fig. 4
Fig. 4

(a) Fully packaged OCT endomicroscope inside a gastrointestinal endoscope. The endomicroscope with compact packaging passes through the accessory channel. (b) Schematic and optical image of forward viewing OCT endomicroscopic catheter. (c) Optical image of a national coin. (d)-(f) time-lapse reconstructed 3D OCT image of the national coin with the detection time of 1 sec (d), 1.5 sec (e) and 2 sec (f). (g)-(h) Ex-vivo OCT images of porcine colon (g) and mouse ear (h). 2D cross-sectional OCT images with 3000 consecutive points along the Lissajous trajectories (subset) were assigned on a specific location of the detection volume and reconstructed to a 3D image (256 x 256 x 995 voxels); mucosa (m), muscularis mucosa (mm), submucosa (sm), and muscularis propria (mp), dermis (d), epidermis (ed). Scale bar; 1 mm.

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