Abstract

In this paper, we describe a technique capable of visualizing mechanical properties at the cellular scale deep in living tissue, by incorporating a gradient-index (GRIN)-lens micro-endoscope into an ultrahigh-resolution optical coherence elastography system. The optical system, after the endoscope, has a lateral resolution of 1.6 µm and an axial resolution of 2.2 µm. Bessel beam illumination and Gaussian mode detection are used to provide an extended depth-of-field of 80 µm, which is a 4-fold improvement over a fully Gaussian beam case with the same lateral resolution. Using this system, we demonstrate quantitative elasticity imaging of a soft silicone phantom containing a stiff inclusion and a freshly excised malignant murine pancreatic tumor. We also demonstrate qualitative strain imaging below the tissue surface on in situ murine muscle. The approach we introduce here can provide high-quality extended-focus images through a micro-endoscope with potential to measure cellular-scale mechanics deep in tissue. We believe this tool is promising for studying biological processes and disease progression in vivo.

© 2017 Optical Society of America

Full Article  |  PDF Article

Corrections

24 October 2017: A typographical correction was made to the author listing.


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2017 (2)

B. F. Kennedy, P. Wijesinghe, and D. D. Sampson, “The emergence of optical elastography in biomedicine,” Nat. Photon. 11, 215–221 (2017).
[Crossref]

K. Larin and D. D. Sampson, “Optical coherence elastography - OCT at work in tissue biomechanics,” Biomed. Opt. Express 8(2), 1172–1202 (2017).
[Crossref] [PubMed]

2016 (3)

A. Curatolo, M. Villiger, D. Lorenser, P. Wijesinghe, A. Fritz, B. F. Kennedy, and D. D. Sampson, “Ultrahigh resolution optical coherence elastography,” Opt. Lett. 41(1), 21–24 (2016).
[Crossref]

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

2015 (2)

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

2014 (2)

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantun Electron. 20(2), 7101217 (2014).

2013 (1)

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

2012 (5)

2011 (2)

2008 (1)

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photon. 2, 39–43 (2008).
[Crossref]

2007 (1)

P. A. Janmey and C. A. McCulloch, “Cell mechanics: integrating cell responses to mechanical stimuli,” Annu. Rev. Biomed. Eng. 9, 1–34 (2007).
[Crossref] [PubMed]

2006 (1)

2005 (2)

H.-J. Butt, B. Cappella, and M. Kappl, “Force measurements with the atomic force microscope: Technique, interpretation and applications,” Surf. Sci. Rep. 59(1–6), 1–152 (2005).
[Crossref]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

2004 (1)

2003 (1)

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5, 57–78 (2003).
[Crossref] [PubMed]

2001 (1)

S. Munevar, Y. Wang, and M. Dembo, “Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts,” Biophys. J.,  80(4), 1744–1757 (2001).
[Crossref] [PubMed]

1998 (3)

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

R. Ganss and D. Hanahan, “Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes,” Cancer Res. 58(20), 4673–4681 (1998).
[PubMed]

J. M. Schmitt, “OCT elastography: imaging microscopic deformation and strain of tissue,” Opt. Express 3(6), 199–211 (1998).
[Crossref] [PubMed]

1996 (1)

R. Muthupillai and R. L. Ehman, “Magnetic resonance elastography,” Nat. Med. 2, 601–603 (1996).
[Crossref] [PubMed]

Brenner, M.

Brown, C. M.

Butt, H.-J.

H.-J. Butt, B. Cappella, and M. Kappl, “Force measurements with the atomic force microscope: Technique, interpretation and applications,” Surf. Sci. Rep. 59(1–6), 1–152 (2005).
[Crossref]

Cappella, B.

H.-J. Butt, B. Cappella, and M. Kappl, “Force measurements with the atomic force microscope: Technique, interpretation and applications,” Surf. Sci. Rep. 59(1–6), 1–152 (2005).
[Crossref]

Chen, Z.

Cheung, E. L. M.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Chin, L.

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

Choi, Myunghwan

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Curatolo, A.

A. Curatolo, M. Villiger, D. Lorenser, P. Wijesinghe, A. Fritz, B. F. Kennedy, and D. D. Sampson, “Ultrahigh resolution optical coherence elastography,” Opt. Lett. 41(1), 21–24 (2016).
[Crossref]

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Dantuono, J. T.

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

Dembo, M.

S. Munevar, Y. Wang, and M. Dembo, “Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts,” Biophys. J.,  80(4), 1744–1757 (2001).
[Crossref] [PubMed]

Dong, L.

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

Duker, J. S.

Ehman, R. L.

R. Muthupillai and R. L. Ehman, “Magnetic resonance elastography,” Nat. Med. 2, 601–603 (1996).
[Crossref] [PubMed]

Emelianov, S. Y.

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Fatemi, M.

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5, 57–78 (2003).
[Crossref] [PubMed]

Flusberg, B. A.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Fowlkes, J. B.

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Fritz, A.

Fujimoto, J. G.

Ganss, R.

R. Ganss and D. Hanahan, “Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes,” Cancer Res. 58(20), 4673–4681 (1998).
[PubMed]

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Greenleaf, J. F.

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5, 57–78 (2003).
[Crossref] [PubMed]

Guo, S.

Hajjarian, Z.

Z. Hajjarian and S. K. Nadkarni, “Evaluating the viscoelastic properties of tissue from laser speckle fluctuations,” Sci. Rep. 2, 316 (2012).
[Crossref] [PubMed]

Hanahan, D.

R. Ganss and D. Hanahan, “Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes,” Cancer Res. 58(20), 4673–4681 (1998).
[PubMed]

Howard, S. S.

Huland, D. M.

Insana, M.

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5, 57–78 (2003).
[Crossref] [PubMed]

Janmey, P. A.

P. A. Janmey and C. A. McCulloch, “Cell mechanics: integrating cell responses to mechanical stimuli,” Annu. Rev. Biomed. Eng. 9, 1–34 (2007).
[Crossref] [PubMed]

Ji, N.

Johansen, N. J.

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Jung, J. C.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Jung, Keehoon

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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]

Kappl, M.

H.-J. Butt, B. Cappella, and M. Kappl, “Force measurements with the atomic force microscope: Technique, interpretation and applications,” Surf. Sci. Rep. 59(1–6), 1–152 (2005).
[Crossref]

Kennedy, B. F.

B. F. Kennedy, P. Wijesinghe, and D. D. Sampson, “The emergence of optical elastography in biomedicine,” Nat. Photon. 11, 215–221 (2017).
[Crossref]

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

A. Curatolo, M. Villiger, D. Lorenser, P. Wijesinghe, A. Fritz, B. F. Kennedy, and D. D. Sampson, “Ultrahigh resolution optical coherence elastography,” Opt. Lett. 41(1), 21–24 (2016).
[Crossref]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantun Electron. 20(2), 7101217 (2014).

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, and D. D. Sampson, “Strain estimation in phase-sensitive optical coherence elastography,” Biomed. Opt. Express 3(8), 1865–1879 (2012).
[Crossref] [PubMed]

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Kennedy, K. M.

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantun Electron. 20(2), 7101217 (2014).

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, and D. D. Sampson, “Strain estimation in phase-sensitive optical coherence elastography,” Biomed. Opt. Express 3(8), 1865–1879 (2012).
[Crossref] [PubMed]

Kim, Jun Ki

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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, Pilhan

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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, Seonghoon

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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]

Ko, T. H.

Koh, S. H.

Kowalczyk, A.

Larin, K.

Latham, B.

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

Lee, W. M.

Lee, Woei Ming

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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]

Lorenser, D.

McCulloch, C. A.

P. A. Janmey and C. A. McCulloch, “Cell mechanics: integrating cell responses to mechanical stimuli,” Annu. Rev. Biomed. Eng. 9, 1–34 (2007).
[Crossref] [PubMed]

McLaughlin, R. A.

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, and D. D. Sampson, “Strain estimation in phase-sensitive optical coherence elastography,” Biomed. Opt. Express 3(8), 1865–1879 (2012).
[Crossref] [PubMed]

Mukai, D.

Munevar, S.

S. Munevar, Y. Wang, and M. Dembo, “Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts,” Biophys. J.,  80(4), 1744–1757 (2001).
[Crossref] [PubMed]

Munro, P. R. T.

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, and D. D. Sampson, “Strain estimation in phase-sensitive optical coherence elastography,” Biomed. Opt. Express 3(8), 1865–1879 (2012).
[Crossref] [PubMed]

Muthupillai, R.

R. Muthupillai and R. L. Ehman, “Magnetic resonance elastography,” Nat. Med. 2, 601–603 (1996).
[Crossref] [PubMed]

Nadkarni, S. K.

Z. Hajjarian and S. K. Nadkarni, “Evaluating the viscoelastic properties of tissue from laser speckle fluctuations,” Sci. Rep. 2, 316 (2012).
[Crossref] [PubMed]

Oberai, A. A.

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

Ouzounov, D. G.

Pavlova, I.

Pillai, R. S.

Piyawattanametha, W.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Rivera, D. R.

Ronald, M.

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

Rudenko, O. V.

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Sampson, D. D.

B. F. Kennedy, P. Wijesinghe, and D. D. Sampson, “The emergence of optical elastography in biomedicine,” Nat. Photon. 11, 215–221 (2017).
[Crossref]

K. Larin and D. D. Sampson, “Optical coherence elastography - OCT at work in tissue biomechanics,” Biomed. Opt. Express 8(2), 1172–1202 (2017).
[Crossref] [PubMed]

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

A. Curatolo, M. Villiger, D. Lorenser, P. Wijesinghe, A. Fritz, B. F. Kennedy, and D. D. Sampson, “Ultrahigh resolution optical coherence elastography,” Opt. Lett. 41(1), 21–24 (2016).
[Crossref]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantun Electron. 20(2), 7101217 (2014).

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, and D. D. Sampson, “Strain estimation in phase-sensitive optical coherence elastography,” Biomed. Opt. Express 3(8), 1865–1879 (2012).
[Crossref] [PubMed]

R. S. Pillai, D. Lorenser, and D. D. Sampson, “Deep-tissue access with confocal fluorescence microendoscopy through hypodermic needles,” Opt. Express 19(8), 7213–7221 (2011).
[Crossref] [PubMed]

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Sarvazyan, A. P.

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Saunders, C. M.

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

Scarcelli, G.

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photon. 2, 39–43 (2008).
[Crossref]

Schmitt, J. M.

Schnitzer, M. J.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Singe, C. C.

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

Sreekumar, P.

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

Srinivasan, V. J.

Swanson, S. D.

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Tien, A.

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, A. Curatolo, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure,” Biomed. Opt. Express 5(7), 2113–2124 (2014).
[Crossref] [PubMed]

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

Villiger, M.

Wang, C.

Wang, K.

Wang, Y.

S. Munevar, Y. Wang, and M. Dembo, “Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts,” Biophys. J.,  80(4), 1744–1757 (2001).
[Crossref] [PubMed]

Webb, W. W.

Wijesinghe, P.

B. F. Kennedy, P. Wijesinghe, and D. D. Sampson, “The emergence of optical elastography in biomedicine,” Nat. Photon. 11, 215–221 (2017).
[Crossref]

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

A. Curatolo, M. Villiger, D. Lorenser, P. Wijesinghe, A. Fritz, B. F. Kennedy, and D. D. Sampson, “Ultrahigh resolution optical coherence elastography,” Opt. Lett. 41(1), 21–24 (2016).
[Crossref]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

Wojtkowski, M.

Xie, T.

Xu, C.

Yun, S. H.

W. M. Lee and S. H. Yun, “Adaptive aberration correction of GRIN lenses for confocal endomicroscopy,” Opt. Lett. 36(23), 4608–4610 (2011).
[Crossref] [PubMed]

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photon. 2, 39–43 (2008).
[Crossref]

Yun, Seok Hyun

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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]

Annu. Rev. Biomed. Eng. (2)

P. A. Janmey and C. A. McCulloch, “Cell mechanics: integrating cell responses to mechanical stimuli,” Annu. Rev. Biomed. Eng. 9, 1–34 (2007).
[Crossref] [PubMed]

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5, 57–78 (2003).
[Crossref] [PubMed]

Biomed. Opt. Express (4)

Biophys. J. (1)

S. Munevar, Y. Wang, and M. Dembo, “Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts,” Biophys. J.,  80(4), 1744–1757 (2001).
[Crossref] [PubMed]

Cancer Res. (2)

R. Ganss and D. Hanahan, “Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes,” Cancer Res. 58(20), 4673–4681 (1998).
[PubMed]

B. F. Kennedy, R. A. McLaughlin, K. M. Kennedy, L. Chin, P. Wijesinghe, A. Curatolo, A. Tien, M. Ronald, B. Latham, C. M. Saunders, and D. D. Sampson, “Investigation of optical coherence microelastography as a method to visualize cancers in human breast tissue,” Cancer Res. 75(16), 3236–3245 (2015).
[Crossref] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

L. Dong, P. Wijesinghe, J. T. Dantuono, D. D. Sampson, P. R. T. Munro, B. F. Kennedy, and A. A. Oberai, “Quantitative compression optical coherence elastography as an inverse elasticity problem,” IEEE J. Sel. Top. Quantum Electron. 22(3), 6802211 (2016).
[Crossref]

IEEE J. Sel. Top. Quantun Electron. (1)

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantun Electron. 20(2), 7101217 (2014).

J. Biomed. Opt. (1)

K. M. Kennedy, R. A. McLaughlin, B. F. Kennedy, A. Tien, B. Latham, C. M. Saunders, and D. D. Sampson, “Needle optical coherence elastography for measurement of microscale mechanical contrast deep within human breast tissues,” J. Biomed. Opt. 18(12), 121510 (2013).
[Crossref] [PubMed]

Nat. Med. (1)

R. Muthupillai and R. L. Ehman, “Magnetic resonance elastography,” Nat. Med. 2, 601–603 (1996).
[Crossref] [PubMed]

Nat. Methods (1)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2, 941–950 (2005).
[Crossref] [PubMed]

Nat. Photon. (2)

B. F. Kennedy, P. Wijesinghe, and D. D. Sampson, “The emergence of optical elastography in biomedicine,” Nat. Photon. 11, 215–221 (2017).
[Crossref]

G. Scarcelli and S. H. Yun, “Confocal Brillouin microscopy for three-dimensional mechanical imaging,” Nat. Photon. 2, 39–43 (2008).
[Crossref]

Nat. Protoc. (1)

Jun Ki Kim, Woei Ming Lee, Pilhan Kim, Myunghwan Choi, Keehoon Jung, Seonghoon Kim, and Seok Hyun 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]

Opt. Express (4)

Opt. Lett. (3)

Sci. Rep. (3)

K. M. Kennedy, L. Chin, R. A. McLaughlin, B. Latham, C. M. Saunders, D. D. Sampson, and B. F. Kennedy, “Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography,” Sci. Rep. 5, 15538 (2015).
[Crossref] [PubMed]

Z. Hajjarian and S. K. Nadkarni, “Evaluating the viscoelastic properties of tissue from laser speckle fluctuations,” Sci. Rep. 2, 316 (2012).
[Crossref] [PubMed]

A. Curatolo, P. R. T. Munro, D. Lorenser, P. Sreekumar, C. C. Singe, B. F. Kennedy, and D. D. Sampson, “Quantifying the influence of Bessel beams on image quality in optical coherence tomography,” Sci. Rep. 6, 23483 (2016).
[Crossref] [PubMed]

Surf. Sci. Rep. (1)

H.-J. Butt, B. Cappella, and M. Kappl, “Force measurements with the atomic force microscope: Technique, interpretation and applications,” Surf. Sci. Rep. 59(1–6), 1–152 (2005).
[Crossref]

Ultrasound Med. Biol. (1)

A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics,” Ultrasound Med. Biol. 24(9), 1419–1435 (1998).
[Crossref]

Other (1)

P. Wijesinghe, N. J. Johansen, A. Curatolo, D. D. Sampson, R. Ganss, and B. F. Kennedy, “Ultrahigh-resolution optical coherence elastography images cellular-scale stiffness of mouse aorta,” Biophys. J. (in press), (2017).

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Figures (6)

Fig. 1
Fig. 1

(a) Schematic of the UHROCE system. DC, dispersion compensation; FC, fiber coupler; GS, galvanometer scanning mirrors; OL, objective lens; SLM, spatial light modulator (angle exaggerated); PBS, polarizing beam splitter; PC, polarization controller; λ/4, quarter-wave plate. (b) Enlarged drawing of the GRIN lens micro-endoscope setup used for phantom and ex vivo tissue measurements. GM, GRIN lens micro-endoscope; GP, glass plate; L, compliant layer; PA, piezoelectric actuator; S, sample. (c) Drawing of the micro-endoscope setup used for the in situ measurement. Figure components are not to scale.

Fig. 2
Fig. 2

Bessel beam profiles before and after the micro-endoscope. En face Bessel beam profile at focus (a) before and (b) after the micro-endoscope. Axial Bessel beam profile (c) before and (e) after the micro-endoscope. Maximum light intensity projection along the axial direction at focus (d) before and (f) after the micro-endoscope. DOF, depth-of-field.

Fig. 3
Fig. 3

PSF characterization. En face OCT image of a particle at focus in a PSF phantom imaged (a) before and (b) after the micro-endoscope; OCT B-scan of a particle at focus in the PSF phantom (c) before and (d) after the micro-endoscope. (e) and (f) SNR profiles along the horizontal and vertical red dashed lines in (a). (h) and (i) SNR profiles along the horizontal and vertical red dashed lines in (b). (g) and (j) SNR profiles along the vertical red dashed line in (c) and (d), respectively. Double-headed arrows are labelled for characterized resolutions in (e)–(j).

Fig. 4
Fig. 4

En face (a) OCM image and (b) quantitative micro-elastogram of the phantom at a depth of 100 µm.

Fig. 5
Fig. 5

En face (a) OCM image and (b) quantitative micro-elastogram of the freshly excised murine pancreatic tumor at a depth of 100 µm. The black arrows indicate a stiff area in the tumor. (c) Photograph of the tumor. The green dashed circle indicates the indented area, which corresponds to the scanning location. The photograph is cropped around the tumor margin. (d) Representative H&E histology at 100 µm depth with an enlarged view of the approximate scan area. C, cancer cells; E, extracellular matrices.

Fig. 6
Fig. 6

En face (a) OCM image and (b) strain micro-elastogram at an imaging depth of 230 µm from the surface of the murine muscle. (c) Photograph of the in situ setup. The red light appears illuminating the sample is the scattering light in the visible wings of the spectrum. PA, piezoelectric actuator.

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