Abstract

Flexible endomicroscopes commonly use coherent fiber bundles with high core densities to facilitate high-resolution in vivo imaging during endoscopic and minimally-invasive procedures. However, under-sampling due to the inter-core spacing limits the spatial resolution, making it difficult to resolve smaller cellular features. Here, we report a compact and rapid piezoelectric transducer (PZT) based bundle-shifting endomicroscopy system in which a super-resolution (SR) image is restored from multiple pixelation-limited images by computational means. A miniaturized PZT tube actuates the fiber bundle behind a GRIN micro-lens and a Delaunay triangulation based algorithm reconstructs an enhanced SR image. To enable real-time cellular-level imaging, imaging is performed using a line-scan confocal laser endomicroscope system with a raw frame rate of 120 fps, delivering up to 2 times spatial resolution improvement for a field of view of 350 µm at a net frame rate of 30 fps. The resolution enhancement is confirmed using resolution phantoms and ex vivo fluorescence endomicroscopy imaging of human breast specimens is demonstrated.

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References

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  26. K. Vyas, M. Hughes, and G.-Z. Yang, “Fiber-shifting endomicroscopy for enhanced resolution imaging,” in “Laser Science,” (Optical Society of America, 2017), pp. JTu2A-79.
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    [PubMed]
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    [Crossref]
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    [Crossref]
  30. P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref]

2018 (1)

2017 (1)

2015 (3)

E. R. Languirand and B. M. Cullum, “Large area super-resolution chemical imaging via rapid dithering of a nanoprobe,” Proc. SPIE 9487, 94870 (2015).
[Crossref]

J. Cheng, Y. Chang, and S.-C. Chen, “Real-time high-resolution fiber bundle based two-photon endomicroscope,” Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. 9304, 54–55 (2015).

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

2014 (1)

A. Shinde and M. V. Matham, “Pixelate removal in an image fiber probe endoscope incorporating comb structure removal methods,” J. Med. Imaging Heal. Informatics 4, 203–211 (2014).
[Crossref]

2013 (1)

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19, 760–771 (2013).
[Crossref]

2012 (2)

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

2011 (1)

2010 (2)

J.-H. Han, J. Lee, and J. U. Kang, “Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging,” Opt. Express 18, 7427–7439 (2010).
[Crossref] [PubMed]

M. Kyrish, R. Kester, R. Richards-Kortum, and T. Tkaczyk, “Improving spatial resolution of a fiber bundle optical biopsy system,” Proc. SPIE 7558, 755807 (2010).
[Crossref]

2008 (1)

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

2007 (3)

2006 (1)

P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
[Crossref]

2005 (1)

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

2004 (1)

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

2003 (2)

S. C. Park, M. K. Park, and M. G. Kang, “Super-resolution image reconstruction: a technical overview,” IEEE Signal Process. Mag. 20, 21–36 (2003).
[Crossref]

D. Capel and A. Zisserman, “Computer vision applied to super resolution,” IEEE Signal Process. Mag. 20, 75–86 (2003).
[Crossref]

2002 (2)

E. J. Seibel and Q. Y. Smithwick, “Unique features of optical scanning single fiber endoscopy,” Lasers Surg. Medicine 30, 177–183 (2002).
[Crossref]

S. Lertrattanapanich and N. K. Bose, “High resolution image formation from low resolution frames using delaunay triangulation,” IEEE Transactions on Image Process. 11, 1427–1441 (2002).
[Crossref]

1997 (1)

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

1993 (1)

1992 (1)

C. J. Chen, “Electromechanical deflections of piezoelectric tubes with quartered electrodes,” Appl. Phys. Lett. 60, 132–134 (1992).
[Crossref]

1991 (1)

K. J. Pienta and D. S. Coffey, “Correlation of nuclear morphometry with progression of breast cancer,” Cancer. 68, 2012–2016 (1991).
[Crossref] [PubMed]

Abrat, B.

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Adler, D. C.

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

Ayache, N.

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Aziz, D.

Barnard, K.

Berier, F.

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

F. Berier and A. Perchant, “Method and system for super-resolution of confocal images acquired through an image guide, and device used for implementing such a method,” US Patent7,646,938 (2010).

Bixler, J. N.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

Blanco, J.

Boppart, S. A.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Bose, N. K.

S. Lertrattanapanich and N. K. Bose, “High resolution image formation from low resolution frames using delaunay triangulation,” IEEE Transactions on Image Process. 11, 1427–1441 (2002).
[Crossref]

Bouma, B. E.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Brezinski, M. E.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Capel, D.

D. Capel and A. Zisserman, “Computer vision applied to super resolution,” IEEE Signal Process. Mag. 20, 75–86 (2003).
[Crossref]

Castle, P.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Cavé, C.

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Chang, T. P.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Chang, Y.

J. Cheng, Y. Chang, and S.-C. Chen, “Real-time high-resolution fiber bundle based two-photon endomicroscope,” Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. 9304, 54–55 (2015).

Chen, C. J.

C. J. Chen, “Electromechanical deflections of piezoelectric tubes with quartered electrodes,” Appl. Phys. Lett. 60, 132–134 (1992).
[Crossref]

Chen, S.-C.

J. Cheng, Y. Chang, and S.-C. Chen, “Real-time high-resolution fiber bundle based two-photon endomicroscope,” Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. 9304, 54–55 (2015).

Chen, Y.

K. Murari, Y. Zhang, S. Li, Y. Chen, M.-J. Li, and X. Li, “Compensation-free, all-fiber-optic, two-photon endomi-croscopy at 1.55 µ m,” Opt. Lett. 36, 1299–1301 (2011).
[Crossref] [PubMed]

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

Cheng, J.

J. Cheng, Y. Chang, and S.-C. Chen, “Real-time high-resolution fiber bundle based two-photon endomicroscope,” Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. 9304, 54–55 (2015).

Chung, E.

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19, 760–771 (2013).
[Crossref]

Coffey, D. S.

K. J. Pienta and D. S. Coffey, “Correlation of nuclear morphometry with progression of breast cancer,” Cancer. 68, 2012–2016 (1991).
[Crossref] [PubMed]

Connolly, J.

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

Cullum, B. M.

E. R. Languirand and B. M. Cullum, “Large area super-resolution chemical imaging via rapid dithering of a nanoprobe,” Proc. SPIE 9487, 94870 (2015).
[Crossref]

Darwiche, H.

Darzi, A.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Delaney, P. M.

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

Dumripatanachod, M.

M. Dumripatanachod and W. Piyawattanametha, “A fast depixelation method of fiber bundle image for an embedded system,” in “Biomedical Engineering International Conference (BMEiCON),” (IEEE, 2015), pp. 1–4.

Fujimoto, J. G.

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

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Genet, M.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Gillenwater, A.

Gmitro, A. F.

Guan, Y.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Hadjiminas, D. J.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Han, J.-H.

Harris, M. R.

M. R. Harris, “Fibre bundle confocal endomicroscope,” US Patent8,057,083 (2011).

Huber, R.

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

Hughes, M.

M. Hughes and G.-Z. Yang, “Line-scanning fiber bundle endomicroscopy with a virtual detector slit,” Biomed. Opt. Express 7, 2257–2268.
[PubMed]

K. Vyas, M. Hughes, and G.-Z. Yang, “Fiber-shifting endomicroscopy for enhanced resolution imaging,” in “Laser Science,” (Optical Society of America, 2017), pp. JTu2A-79.

Hughes, M. R.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Jabbour, J. M.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

Kang, J. U.

Kang, M. G.

S. C. Park, M. K. Park, and M. G. Kang, “Super-resolution image reconstruction: a technical overview,” IEEE Signal Process. Mag. 20, 21–36 (2003).
[Crossref]

Kester, R.

M. Kyrish, R. Kester, R. Richards-Kortum, and T. Tkaczyk, “Improving spatial resolution of a fiber bundle optical biopsy system,” Proc. SPIE 7558, 755807 (2010).
[Crossref]

Kiesslich, R.

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

Kyrish, M.

M. Kyrish, R. Kester, R. Richards-Kortum, and T. Tkaczyk, “Improving spatial resolution of a fiber bundle optical biopsy system,” Proc. SPIE 7558, 755807 (2010).
[Crossref]

Lacombe, F.

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

Laemmel, E.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

Languirand, E. R.

E. R. Languirand and B. M. Cullum, “Large area super-resolution chemical imaging via rapid dithering of a nanoprobe,” Proc. SPIE 9487, 94870 (2015).
[Crossref]

Le Gargasson, J.-F.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

Le Goualher, G.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Lee, D.

Lee, J.

Leff, D. R.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Lertrattanapanich, S.

S. Lertrattanapanich and N. K. Bose, “High resolution image formation from low resolution frames using delaunay triangulation,” IEEE Transactions on Image Process. 11, 1427–1441 (2002).
[Crossref]

Li, M.-J.

Li, S.

Li, X.

Liang, R.

Liao, W.-C.

Maitland, K. C.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

Matham, M. V.

A. Shinde and M. V. Matham, “Pixelate removal in an image fiber probe endoscope incorporating comb structure removal methods,” J. Med. Imaging Heal. Informatics 4, 203–211 (2014).
[Crossref]

McLaren, W. J.

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

Meining, A.

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

Muldoon, T. J.

Murari, K.

Neurath, M. F.

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

Nida, D. L.

Oh, G.

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19, 760–771 (2013).
[Crossref]

Park, M. K.

S. C. Park, M. K. Park, and M. G. Kang, “Super-resolution image reconstruction: a technical overview,” IEEE Signal Process. Mag. 20, 21–36 (2003).
[Crossref]

Park, S. C.

S. C. Park, M. K. Park, and M. G. Kang, “Super-resolution image reconstruction: a technical overview,” IEEE Signal Process. Mag. 20, 21–36 (2003).
[Crossref]

Perchant, A.

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

F. Berier and A. Perchant, “Method and system for super-resolution of confocal images acquired through an image guide, and device used for implementing such a method,” US Patent7,646,938 (2010).

Pienta, K. J.

K. J. Pienta and D. S. Coffey, “Correlation of nuclear morphometry with progression of breast cancer,” Cancer. 68, 2012–2016 (1991).
[Crossref] [PubMed]

Pierce, M. C.

Pitris, C.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Piyawattanametha, W.

M. Dumripatanachod and W. Piyawattanametha, “A fast depixelation method of fiber bundle image for an embedded system,” in “Biomedical Engineering International Conference (BMEiCON),” (IEEE, 2015), pp. 1–4.

Polglase, A. L.

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

Qiao, Y.-L.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Quinn, M. K.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Ra, H.

Ramakrishnan, R.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Richards-Kortum, R.

Saldua, M. A.

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

Schmitt, J.

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

Seibel, E. J.

E. J. Seibel and Q. Y. Smithwick, “Unique features of optical scanning single fiber endoscopy,” Lasers Surg. Medicine 30, 177–183 (2002).
[Crossref]

Shadfan, A.

Shao, J.

Shin, H.-J.

Shinde, A.

A. Shinde and M. V. Matham, “Pixelate removal in an image fiber probe endoscope incorporating comb structure removal methods,” J. Med. Imaging Heal. Informatics 4, 203–211 (2014).
[Crossref]

Shousha, S.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Skinner, S. A.

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

Smithwick, Q. Y.

E. J. Seibel and Q. Y. Smithwick, “Unique features of optical scanning single fiber endoscopy,” Lasers Surg. Medicine 30, 177–183 (2002).
[Crossref]

Solgaard, O.

Southern, J. F.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Süsstrunk, S.

P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
[Crossref]

Tearney, G. J.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Tkaczyk, T.

M. Kyrish, R. Kester, R. Richards-Kortum, and T. Tkaczyk, “Improving spatial resolution of a fiber bundle optical biopsy system,” Proc. SPIE 7558, 755807 (2010).
[Crossref]

Tkaczyk, T. S.

Vandewalle, P.

P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
[Crossref]

Vercauteren, T.

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

Vetterli, M.

P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
[Crossref]

Vicaut, E.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

Viellerobe, B.

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

Vyas, K.

K. Vyas, M. Hughes, and G.-Z. Yang, “Fiber-shifting endomicroscopy for enhanced resolution imaging,” in “Laser Science,” (Optical Society of America, 2017), pp. JTu2A-79.

Williams, M. D.

Yang, G.-Z.

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

K. Vyas, M. Hughes, and G.-Z. Yang, “Fiber-shifting endomicroscopy for enhanced resolution imaging,” in “Laser Science,” (Optical Society of America, 2017), pp. JTu2A-79.

M. Hughes and G.-Z. Yang, “Line-scanning fiber bundle endomicroscopy with a virtual detector slit,” Biomed. Opt. Express 7, 2257–2268.
[PubMed]

Yun, S. H.

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19, 760–771 (2013).
[Crossref]

Zhang, W.-H.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Zhang, X.

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Zhang, Y.

Zisserman, A.

D. Capel and A. Zisserman, “Computer vision applied to super resolution,” IEEE Signal Process. Mag. 20, 75–86 (2003).
[Crossref]

Annals Biomed. Eng. (1)

J. M. Jabbour, M. A. Saldua, J. N. Bixler, and K. C. Maitland, “Confocal endomicroscopy: instrumentation and medical applications,” Annals Biomed. Eng. 40, 378–397 (2012).
[Crossref]

Appl. Phys. Lett. (1)

C. J. Chen, “Electromechanical deflections of piezoelectric tubes with quartered electrodes,” Appl. Phys. Lett. 60, 132–134 (1992).
[Crossref]

Biomed. Opt. Express (2)

Breast Cancer Res. Treat. (1)

T. P. Chang, D. R. Leff, S. Shousha, D. J. Hadjiminas, R. Ramakrishnan, M. R. Hughes, G.-Z. Yang, and A. Darzi, “Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Res. Treat. 153, 299–310 (2015).
[Crossref] [PubMed]

Cancer Prev. Res. (1)

M. C. Pierce, Y. Guan, M. K. Quinn, X. Zhang, W.-H. Zhang, Y.-L. Qiao, P. Castle, and R. Richards-Kortum, “A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer,” Cancer Prev. Res. 5, 1273–1279 (2012).
[Crossref]

Cancer. (1)

K. J. Pienta and D. S. Coffey, “Correlation of nuclear morphometry with progression of breast cancer,” Cancer. 68, 2012–2016 (1991).
[Crossref] [PubMed]

Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. (1)

J. Cheng, Y. Chang, and S.-C. Chen, “Real-time high-resolution fiber bundle based two-photon endomicroscope,” Endosc. Microsc. X; Opt. Tech. Pulm. Medicine II. 9304, 54–55 (2015).

EURASIP J. on Adv. Signal Process. (1)

P. Vandewalle, S. Süsstrunk, and M. Vetterli, “A frequency domain approach to registration of aliased images with application to super-resolution,” EURASIP J. on Adv. Signal Process. 2006, 071459 (2006).
[Crossref]

Gastrointest. Endosc. (1)

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

IEEE Signal Process. Mag. (2)

D. Capel and A. Zisserman, “Computer vision applied to super resolution,” IEEE Signal Process. Mag. 20, 75–86 (2003).
[Crossref]

S. C. Park, M. K. Park, and M. G. Kang, “Super-resolution image reconstruction: a technical overview,” IEEE Signal Process. Mag. 20, 21–36 (2003).
[Crossref]

IEEE Transactions on Image Process. (1)

S. Lertrattanapanich and N. K. Bose, “High resolution image formation from low resolution frames using delaunay triangulation,” IEEE Transactions on Image Process. 11, 1427–1441 (2002).
[Crossref]

J. Med. Imaging Heal. Informatics (1)

A. Shinde and M. V. Matham, “Pixelate removal in an image fiber probe endoscope incorporating comb structure removal methods,” J. Med. Imaging Heal. Informatics 4, 203–211 (2014).
[Crossref]

J. Vasc. Res. (1)

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (cell-viZio) facilitates extended imaging in the field of microcirculation,” J. Vasc. Res. 41, 400–411 (2004).
[Crossref] [PubMed]

Lasers Surg. Medicine (1)

E. J. Seibel and Q. Y. Smithwick, “Unique features of optical scanning single fiber endoscopy,” Lasers Surg. Medicine 30, 177–183 (2002).
[Crossref]

Nat. Photon. (1)

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

Opt. Express (3)

Opt. Fiber Technol. (1)

G. Oh, E. Chung, and S. H. Yun, “Optical fibers for high-resolution in vivo microendoscopic fluorescence imaging,” Opt. Fiber Technol. 19, 760–771 (2013).
[Crossref]

Opt. Lett. (3)

Proc. SPIE (3)

M. Kyrish, R. Kester, R. Richards-Kortum, and T. Tkaczyk, “Improving spatial resolution of a fiber bundle optical biopsy system,” Proc. SPIE 7558, 755807 (2010).
[Crossref]

T. Vercauteren, A. Meining, F. Lacombe, and A. Perchant, “Real time autonomous video image registration for endomicroscopy: fighting the compromises,” Proc. SPIE 6861, 68610 (2008).
[Crossref]

E. R. Languirand and B. M. Cullum, “Large area super-resolution chemical imaging via rapid dithering of a nanoprobe,” Proc. SPIE 9487, 94870 (2015).
[Crossref]

Science (1)

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science.  276, 2037–2039 (1997).
[Crossref] [PubMed]

Other (5)

G. Le Goualher, A. Perchant, M. Genet, C. Cavé, B. Viellerobe, F. Berier, B. Abrat, and N. Ayache, “Towards optical biopsies with an integrated fibered confocal fluorescence microscope,” in “International Conference on Medical Image Computing and Computer-Assisted Intervention,” (Springer, 2004), pp. 761–768.

M. Dumripatanachod and W. Piyawattanametha, “A fast depixelation method of fiber bundle image for an embedded system,” in “Biomedical Engineering International Conference (BMEiCON),” (IEEE, 2015), pp. 1–4.

M. R. Harris, “Fibre bundle confocal endomicroscope,” US Patent8,057,083 (2011).

F. Berier and A. Perchant, “Method and system for super-resolution of confocal images acquired through an image guide, and device used for implementing such a method,” US Patent7,646,938 (2010).

K. Vyas, M. Hughes, and G.-Z. Yang, “Fiber-shifting endomicroscopy for enhanced resolution imaging,” in “Laser Science,” (Optical Society of America, 2017), pp. JTu2A-79.

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Figures (7)

Fig. 1
Fig. 1 Schematics of (a) the line-scan confocal laser endomicroscopy (LS-CLE) system with (b) fiber-shifting distal probe. The proximal face of the fiber bundle is placed at the focal plane of the LS-CLE and the distal end is actuated by a PZT tube behind a GRIN lens with 1.92X magnification. (c) A photograph of the assembled 3D printed probe holder tube with 5 mm outer diameter. A UK one pound coin is shown for scale.
Fig. 2
Fig. 2 (a) PZT characterization test: Optical setup for illuminating a single core of the fiber bundle and estimating the tip deflection by tracking the position of the centroid of the focused spot on the CCD camera. Objective1 is microscope objective with 40X magnification and Objective2 is with 20X magnification. (b) Schematics of PZT driver circuit. (c) 2-D plot of fiber bundle deflection versus applied voltage on the PZT electrode pair.
Fig. 3
Fig. 3 Sequence of steps illustrating Delaunay triangulation based reconstruction of SR image from a set of fiber-bundle pixelation limited LR image frames
Fig. 4
Fig. 4 Cropped images of USAF resolution target back-illuminated by a green LED, with fiber shifting motion performed using a translation stage. Large images show Group (G) 7, Elements (E) 3–6, and all elements of Group 8 and 9. Smaller zoomed images show G7,E6, a 2-D plot of the intensities of pixels along the line segment shown by a white line on G7,E6, and the numerical ‘8’. (a) Image acquired with the LS-CLE system and 1.92X GRIN lens (no fiber bundle). (b) Raw experimental LR input image acquired with a fiber bundle and 1.92X GRIN lens. (c–e) Image reconstructed by (c) Gaussian smoothing (σ = 1.7 pixels), (d) Gaussian smoothing with pre histogram equalization and (e) DT algorithm on a single LR image. The respective SR images reconstructed using the proposed method are shown for (f) a 1-D shift pattern where 2 images are acquired with shift of 2.24 µm, (g) a 2-D shift pattern where 4 images are acquired in a square pattern with a shift of 2.24 µm, and (h) a 2-D shift pattern where 8 images are acquired with a 1.12 µm inter-image shift. (i) Single un-cropped image representing all elements of groups 6–9 of USAF target reconstructed using the DT algorithm and 2×2 pattern. Full field of view of each acquired image (in white circle) is 350 µm. Region of interest (marked in red) corresponds to image (g). The scale bar is 10 µm.
Fig. 5
Fig. 5 (a) Square wave modulation contrast obtained by applying the DT algorithm on the average of 4 frames and the proposed SR method. This is compared with imaging through the 1.92X GRIN lens optical system with no imaging bundle. Image of USAF target showing all elements of Groups 8 and 9, reconstructed using the proposed method where fiber shifts are generated using (b) PZT scanner and (c) motorized translation stage. (d) Shows 2-D graph of the intensities of pixels along a line segment on G8, E2-6. Scale bar is 10 µm.
Fig. 6
Fig. 6 Results from imaging lens tissue paper using four images with a 2×2 square shift pattern, showing (a) single raw acquired LR image, (b) reconstruction by Gaussian smoothing on a single LR image, (c) reconstruction by DT algorithm on a single LR image, (d) reconstruction by DT algorithm on the average of 4 shifted LR images, (e) reconstruction using the proposed SR method and (f) un-cropped images of single LR frame and SR image reconstructed using the proposed method. For (a)–(e), images are cropped to 233×233 pixels for better visualization. Zoomed insets (3.1X magnification) correspond to a small area where two lens paper fibers overlap. (g) Plot of pixel intensity along a line segment shown on the insets. Image contrast values are calculated at *peak-1 and **peak-2. The scale bar is 10 µm.
Fig. 7
Fig. 7 Results from imaging adipose cells of human breast tissue using four images with a 2×2 square shift pattern, showing (a) raw single acquired LR image, (b) reconstruction by Gaussian smoothing on a single LR image, (c) reconstruction by DT algorithm on a single LR image, (d) reconstruction by DT algorithm on the average of 4 images, (e) reconstruction using the proposed SR method and (f) un-cropped images of single LR frame and SR image reconstructed using the proposed method, with field of view of 350 µm. For (a)–(e), images are cropped to 233×233 pixels for better visualization. Zoomed insets (3.1X magnification) correspond to a small area containing adjacent nuclei on the borders of adipose cells.(g) Plot of pixel intensity along a line shown in the insets. Image contrast is calculated at *peak-1 and **peak-2. The scale bar is 10 µm.

Equations (4)

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Δ y = 2 2 d 31 V y L 2 π ( D + h ) h
F 2 ( u , v ) = e 2 π i ( u T Δ x + v T Δ y ) F 1 ( u , v )
b i = A i A 1 + A 2 + A 3 w h e r e i = 1 , 2 , 3
I p = b 1 I C , 1 + b 2 I C , 2 + b 3 I C , 3

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