Abstract

We present an automated, label-free method for lymphangiography of cutaneous lymphatic vessels in humans in vivo using optical coherence tomography (OCT). This method corrects for the variation in OCT signal due to the confocal function and sensitivity fall-off of a spectral-domain OCT system and utilizes a single-scattering model to compensate for A-scan signal attenuation to enable reliable thresholding of lymphatic vessels. A segment-joining algorithm is then incorporated into the method to mitigate partial-volume effects with small vessels. The lymphatic vessel images are augmented with images of the blood vessel network, acquired from the speckle decorrelation with additional weighting to differentiate blood vessels from the observed high decorrelation in lymphatic vessels. We demonstrate the method with longitudinal scans of human burn scar patients undergoing ablative fractional laser treatment, showing the visualization of the cutaneous lymphatic and blood vessel networks.

© 2016 Optical Society of America

Full Article  |  PDF Article
OSA Recommended Articles
Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

Mengyang Liu, Zhe Chen, Behrooz Zabihian, Christoph Sinz, Edward Zhang, Paul C. Beard, Laurin Ginner, Erich Hoover, Micheal P. Minneman, Rainer A. Leitgeb, Harald Kittler, and Wolfgang Drexler
Biomed. Opt. Express 7(9) 3390-3402 (2016)

In vivo tissue injury mapping using optical coherence tomography based methods

Utku Baran, Yuandong Li, and Ruikang K. Wang
Appl. Opt. 54(21) 6448-6453 (2015)

References

  • View by:
  • |
  • |
  • |

  1. R. Huggenberger and M. Detmar, “The cutaneous vascular system in chronic skin inflammation,” J. Investig. Dermatol. Symp. Proc. 15(1), 24–32 (2011).
    [Crossref] [PubMed]
  2. A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
    [Crossref] [PubMed]
  3. F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
    [Crossref] [PubMed]
  4. C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
    [Crossref] [PubMed]
  5. S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
    [Crossref] [PubMed]
  6. R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
    [Crossref] [PubMed]
  7. B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
    [Crossref] [PubMed]
  8. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
    [Crossref] [PubMed]
  9. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
    [Crossref] [PubMed]
  10. J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
    [Crossref] [PubMed]
  11. Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
    [Crossref] [PubMed]
  12. C. Blatter, J. Weingast, A. Alex, B. Grajciar, W. Wieser, W. Drexler, R. Huber, and R. A. Leitgeb, “In situ structural and microangiographic assessment of human skin lesions with high-speed OCT,” Biomed. Opt. Express 3(10), 2636–2646 (2012).
    [Crossref] [PubMed]
  13. Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
    [Crossref] [PubMed]
  14. J. M. Schmitt, A. Knüttel, and R. F. Bonner, “Measurement of optical properties of biological tissues by low-coherence reflectometry,” Appl. Opt. 32(30), 6032–6042 (1993).
    [Crossref] [PubMed]
  15. Z. Zhi, Y. Jung, and R. K. Wang, “Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo,” Opt. Lett. 37(5), 812–814 (2012).
    [Crossref] [PubMed]
  16. S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
    [Crossref] [PubMed]
  17. U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
    [Crossref] [PubMed]
  18. V. Ratan, Handbook of Human Physiology (Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, 2004).
  19. T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
    [Crossref] [PubMed]
  20. P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
    [Crossref] [PubMed]
  21. A. Zhang, Q. Zhang, and R. K. Wang, “Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography,” Biomed. Opt. Express 6(10), 4130–4143 (2015).
    [Crossref] [PubMed]
  22. L. Scolaro, R. A. McLaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3(2), 366–379 (2012).
    [Crossref] [PubMed]
  23. P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
    [Crossref] [PubMed]
  24. C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).
  25. M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
    [Crossref] [PubMed]
  26. R. Ogniewicz and M. Ilg, “Voronoi skeletons: theory and applications,” in Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (1992), pp. 63–69.
  27. Y. M. Liew, R. A. McLaughlin, F. M. Wood, and D. D. Sampson, “Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker,” Biomed. Opt. Express 3(8), 1774–1786 (2012).
    [Crossref] [PubMed]
  28. M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
    [PubMed]
  29. M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
    [PubMed]
  30. A. J. Singer and R. A. F. Clark, “Cutaneous wound healing,” N. Engl. J. Med. 341(10), 738–746 (1999).
    [Crossref] [PubMed]
  31. O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
    [Crossref] [PubMed]
  32. M. Skobe and M. Detmar, “Structure, function, and molecular control of the skin lymphatic system,” J. Investig. Dermatol. Symp. Proc. 5(1), 14–19 (2000).
    [Crossref] [PubMed]
  33. C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
    [Crossref] [PubMed]

2016 (4)

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

2015 (1)

2013 (2)

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

2012 (5)

2011 (3)

R. Huggenberger and M. Detmar, “The cutaneous vascular system in chronic skin inflammation,” J. Investig. Dermatol. Symp. Proc. 15(1), 24–32 (2011).
[Crossref] [PubMed]

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
[Crossref] [PubMed]

2010 (2)

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
[Crossref] [PubMed]

2009 (2)

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

2007 (3)

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[Crossref] [PubMed]

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
[Crossref] [PubMed]

2006 (1)

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

2001 (1)

S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
[Crossref] [PubMed]

2000 (1)

M. Skobe and M. Detmar, “Structure, function, and molecular control of the skin lymphatic system,” J. Investig. Dermatol. Symp. Proc. 5(1), 14–19 (2000).
[Crossref] [PubMed]

1999 (1)

A. J. Singer and R. A. F. Clark, “Cutaneous wound healing,” N. Engl. J. Med. 341(10), 738–746 (1999).
[Crossref] [PubMed]

1996 (1)

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

1993 (1)

1992 (1)

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[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, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Alex, A.

Altmeyer, P.

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

Bacharach, S. L.

M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
[Crossref] [PubMed]

Baran, U.

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

Bartlett, L. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Becker, F.

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Blatter, C.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

C. Blatter, J. Weingast, A. Alex, B. Grajciar, W. Wieser, W. Drexler, R. Huber, and R. A. Leitgeb, “In situ structural and microangiographic assessment of human skin lesions with high-speed OCT,” Biomed. Opt. Express 3(10), 2636–2646 (2012).
[Crossref] [PubMed]

Bollinger, A.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Bonner, R. F.

Borud, L. J.

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

Bouma, B. E.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Brorson, H.

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

Buvat, I.

M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
[Crossref] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Chen, X.

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

Choyke, P. L.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Clark, R. A. F.

A. J. Singer and R. A. F. Clark, “Cutaneous wound healing,” N. Engl. J. Med. 341(10), 738–746 (1999).
[Crossref] [PubMed]

Corot, C.

S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
[Crossref] [PubMed]

Costanzo, U.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

de la Zerda, A.

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

Debatin, J. F.

S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
[Crossref] [PubMed]

Detmar, M.

R. Huggenberger and M. Detmar, “The cutaneous vascular system in chronic skin inflammation,” J. Investig. Dermatol. Symp. Proc. 15(1), 24–32 (2011).
[Crossref] [PubMed]

M. Skobe and M. Detmar, “Structure, function, and molecular control of the skin lymphatic system,” J. Investig. Dermatol. Symp. Proc. 5(1), 14–19 (2000).
[Crossref] [PubMed]

Drexler, W.

Enfield, J.

Es’haghian, S.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

Fischer, M.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Franzeck, U. K.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Fujimoto, J. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Fukumura, D.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Gambichler, T.

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

Gao, F.

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

Gong, P.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

Grajciar, B.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Gruber, A.

Hanson, S. R.

Harms, K. A.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Herrig, I.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

Hoffmann, K.

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

Hoffmann, U.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Huber, R.

Huggenberger, R.

R. Huggenberger and M. Detmar, “The cutaneous vascular system in chronic skin inflammation,” J. Investig. Dermatol. Symp. Proc. 15(1), 24–32 (2011).
[Crossref] [PubMed]

Hurst, S.

Ilg, M.

R. Ogniewicz and M. Ilg, “Voronoi skeletons: theory and applications,” in Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (1992), pp. 63–69.

Jacques, S. L.

Jain, R. K.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Jonathan, E.

Jones, D.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

Jung, Y.

Z. Zhi, Y. Jung, and R. K. Wang, “Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo,” Opt. Lett. 37(5), 812–814 (2012).
[Crossref] [PubMed]

Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
[Crossref] [PubMed]

Kalkan, G.

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

Kennedy, B. F.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

Kim, C.

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

Klyen, B. R.

Knüttel, A.

Kobayashi, H.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Kosaka, N.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Lanning, R. M.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Leahy, M.

Leitgeb, R. A.

Liba, O.

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

Liew, Y. M.

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, F. M. Wood, and D. D. Sampson, “Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker,” Biomed. Opt. Express 3(8), 1774–1786 (2012).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Lu, G.

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

Lucarelli, R. T.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Ma, Z.

Matip, R.

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

McLaughlin, R. A.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, F. M. Wood, and D. D. Sampson, “Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker,” Biomed. Opt. Express 3(8), 1774–1786 (2012).
[Crossref] [PubMed]

L. Scolaro, R. A. McLaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3(2), 366–379 (2012).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

Meijer, E. F. J.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

Moussa, G.

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

Munn, L. L.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Munro, P. R. T.

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Murray, A.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

Nam, A. S.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

Niu, G.

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

Ogawa, M.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Ogniewicz, R.

R. Ogniewicz and M. Ilg, “Voronoi skeletons: theory and applications,” in Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (1992), pp. 63–69.

Padera, T. P.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Qi, X.

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

Qin, J.

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

Qin, W.

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

Rea, S.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

Robbins, P. D.

Ruehm, S. G.

S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
[Crossref] [PubMed]

Sampson, D. D.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

L. Scolaro, R. A. McLaughlin, B. R. Klyen, B. A. Wood, P. D. Robbins, C. M. Saunders, S. L. Jacques, and D. D. Sampson, “Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography,” Biomed. Opt. Express 3(2), 366–379 (2012).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, F. M. Wood, and D. D. Sampson, “Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker,” Biomed. Opt. Express 3(8), 1774–1786 (2012).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

Saunders, C. M.

Schiesser, M.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

Schmitt, J. M.

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Scolaro, L.

Sen, D.

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

Shore, A.

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Singer, A. J.

A. J. Singer and R. A. F. Clark, “Cutaneous wound healing,” N. Engl. J. Med. 341(10), 738–746 (1999).
[Crossref] [PubMed]

Skobe, M.

M. Skobe and M. Detmar, “Structure, function, and molecular control of the skin lymphatic system,” J. Investig. Dermatol. Symp. Proc. 5(1), 14–19 (2000).
[Crossref] [PubMed]

Slavin, S. A.

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

Song, K. H.

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

SoRelle, E. D.

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

Soret, M.

M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
[Crossref] [PubMed]

Spiegel, M.

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Stylianopoulos, T.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Tearney, G. J.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Turkbey, B.

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Tyrrell, J. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Vakoc, B. J.

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Vesti, B.

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Wang, L. V.

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

Wang, R. K.

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

A. Zhang, Q. Zhang, and R. K. Wang, “Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography,” Biomed. Opt. Express 6(10), 4130–4143 (2015).
[Crossref] [PubMed]

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

Z. Zhi, Y. Jung, and R. K. Wang, “Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo,” Opt. Lett. 37(5), 812–814 (2012).
[Crossref] [PubMed]

Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
[Crossref] [PubMed]

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[Crossref] [PubMed]

Warren, A. G.

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

Weingast, J.

Wen, S.

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

Wieser, W.

Wood, B. A.

Wood, F. M.

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, F. M. Wood, and D. D. Sampson, “Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker,” Biomed. Opt. Express 3(8), 1774–1786 (2012).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

Yousefi, S.

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

Zhang, A.

Zhang, F.

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

Zhang, Q.

Zhi, Z.

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

Z. Zhi, Y. Jung, and R. K. Wang, “Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo,” Opt. Lett. 37(5), 812–814 (2012).
[Crossref] [PubMed]

Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
[Crossref] [PubMed]

Am. J. Physiol. (2)

M. Fischer, U. K. Franzeck, I. Herrig, U. Costanzo, S. Wen, M. Schiesser, U. Hoffmann, and A. Bollinger, “Flow velocity of single lymphatic capillaries in human skin,” Am. J. Physiol. 270(1 Pt 2), H358–H363 (1996).
[PubMed]

M. Spiegel, B. Vesti, A. Shore, U. K. Franzeck, F. Becker, and A. Bollinger, “Pressure of lymphatic capillaries in human skin,” Am. J. Physiol. 262(4 Pt 2), H1208–H1210 (1992).
[PubMed]

Ann. Plast. Surg. (1)

A. G. Warren, H. Brorson, L. J. Borud, and S. A. Slavin, “Lymphedema: a comprehensive review,” Ann. Plast. Surg. 59(4), 464–472 (2007).
[Crossref] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (5)

J. Biomed. Opt. (4)

P. Gong, R. A. McLaughlin, Y. M. Liew, P. R. T. Munro, F. M. Wood, and D. D. Sampson, “Assessment of human burn scars with optical coherence tomography by imaging the attenuation coefficient of tissue after vascular masking,” J. Biomed. Opt. 19(2), 021111 (2013).
[Crossref] [PubMed]

Y. Jung, Z. Zhi, and R. K. Wang, “Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo,” J. Biomed. Opt. 15(5), 050501 (2010).
[Crossref] [PubMed]

Y. M. Liew, R. A. McLaughlin, P. Gong, F. M. Wood, and D. D. Sampson, “In vivo assessment of human burn scars through automated quantification of vascularity using optical coherence tomography,” J. Biomed. Opt. 18(6), 061213 (2012).
[Crossref] [PubMed]

S. Yousefi, J. Qin, Z. Zhi, and R. K. Wang, “Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters,” J. Biomed. Opt. 18(8), 086004 (2013).
[Crossref] [PubMed]

J. Biophotonics (1)

P. Gong, S. Es’haghian, K. A. Harms, A. Murray, S. Rea, B. F. Kennedy, F. M. Wood, D. D. Sampson, and R. A. McLaughlin, “Optical coherence tomography for longitudinal monitoring of vasculature in scars treated with laser fractionation,” J. Biophotonics 9(6), 626–636 (2016).
[Crossref] [PubMed]

J. Dermatol. Sci. (1)

T. Gambichler, R. Matip, G. Moussa, P. Altmeyer, and K. Hoffmann, “In vivo data of epidermal thickness evaluated by optical coherence tomography: effects of age, gender, skin type, and anatomic site,” J. Dermatol. Sci. 44(3), 145–152 (2006).
[Crossref] [PubMed]

J. Investig. Dermatol. Symp. Proc. (2)

M. Skobe and M. Detmar, “Structure, function, and molecular control of the skin lymphatic system,” J. Investig. Dermatol. Symp. Proc. 5(1), 14–19 (2000).
[Crossref] [PubMed]

R. Huggenberger and M. Detmar, “The cutaneous vascular system in chronic skin inflammation,” J. Investig. Dermatol. Symp. Proc. 15(1), 24–32 (2011).
[Crossref] [PubMed]

J. Nucl. Med. (1)

M. Soret, S. L. Bacharach, and I. Buvat, “Partial-volume effect in PET tumor imaging,” J. Nucl. Med. 48(6), 932–945 (2007).
[Crossref] [PubMed]

Lymphat. Res. Biol. (1)

R. T. Lucarelli, M. Ogawa, N. Kosaka, B. Turkbey, H. Kobayashi, and P. L. Choyke, “New approaches to lymphatic imaging,” Lymphat. Res. Biol. 7(4), 205–214 (2009).
[Crossref] [PubMed]

Mol. Imaging Biol. (1)

F. Zhang, G. Niu, G. Lu, and X. Chen, “Preclinical lymphatic imaging,” Mol. Imaging Biol. 13(4), 599–612 (2011).
[Crossref] [PubMed]

N. Engl. J. Med. (1)

A. J. Singer and R. A. F. Clark, “Cutaneous wound healing,” N. Engl. J. Med. 341(10), 738–746 (1999).
[Crossref] [PubMed]

Nat. Med. (1)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Radiology (2)

C. Kim, K. H. Song, F. Gao, and L. V. Wang, “Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats--volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging,” Radiology 255(2), 442–450 (2010).
[Crossref] [PubMed]

S. G. Ruehm, C. Corot, and J. F. Debatin, “Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits,” Radiology 218(3), 664–669 (2001).
[Crossref] [PubMed]

Sci. Rep. (3)

U. Baran, W. Qin, X. Qi, G. Kalkan, and R. K. Wang, “OCT-based label-free in vivo lymphangiography within human skin and areola,” Sci. Rep. 6, 21122 (2016).
[Crossref] [PubMed]

O. Liba, E. D. SoRelle, D. Sen, and A. de la Zerda, “Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging,” Sci. Rep. 6, 23337 (2016).
[Crossref] [PubMed]

C. Blatter, E. F. J. Meijer, A. S. Nam, D. Jones, B. E. Bouma, T. P. Padera, and B. J. Vakoc, “In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography,” Sci. Rep. 6, 29035 (2016).
[Crossref] [PubMed]

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

Other (3)

V. Ratan, Handbook of Human Physiology (Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, 2004).

R. Ogniewicz and M. Ilg, “Voronoi skeletons: theory and applications,” in Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (1992), pp. 63–69.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Supplementary Material (4)

NameDescription
» Visualization 1: MP4 (5620 KB)      Animation of the three-dimensional lymphatic vessels
» Visualization 2: MP4 (3867 KB)      Animation of the three-dimensional lymphatic vessels
» Visualization 3: MP4 (5031 KB)      Animation of the three-dimensional lymphatic vessels
» Visualization 4: MP4 (3538 KB)      Animation of the three-dimensional lymphatic vessels

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (7)

Fig. 1
Fig. 1

Characteristic of lymphatic vessels in OCT signal. (a) En face OCT image of scar tissue by projecting the minimum intensity from 100 µm to 300 µm below the scar surface after correction of the tissue refractive index (1.43) [19]. (b) and (c) Averaged A-scan, respectively, from a blood and lymphatic vessel region labelled by the blue arrows in (a). (d) The attenuation-compensated signal of the data in the dashed rectangle in (c) after smoothing in the cross-sectional plane to reduce speckle and intensity compensation using calibration scans from a homogenous phantom, as described in Section 3. Scale bar in (a): 500 µm.

Fig. 2
Fig. 2

Characteristic of lymphatic vessels in speckle decorrelation. (a) and (c) Cross-sectional image of the raw OCT signal and the resulting speckle decorrelation of the scar tissue in Fig. 1. (b) and (d) Magnified images of the regions in the dashed rectangles in (a) and (c). L1 and L2: lymphatic vessels; B1: blood vessel. Scale bars in (a) and (c): 250 µm; (b) and (d): 100 µm.

Fig. 3
Fig. 3

Lymphatic vessel imaging method. Processing flow diagram (a) to segment lymphatic vessels (blue boxes) and blood vessels (red boxes) in OCT scans. (b) An averaged A-scan from the low-scattering phantom used for correction. (c) Partial-volume effects on a small lymphatic vessel in the minimum projection image of the OCT signal are indicated by the red arrows. (d) and (e) Projection images of the segmented lymphatic vessels before and after applying the segment-joining algorithm. Scale bars: 200 µm.

Fig. 4
Fig. 4

Timing of the laser treatments (green bars) and OCT scanning (blue bars) of Patients 1 (above the time axis) and 2 (below the time axis).

Fig. 5
Fig. 5

Lymphatic and blood vessel imaging of a scar on Patient 1. (a) Photograph of the scar. (b) and (c) Projection images of the lymphatic and blood vessels to a depth of 400 µm below scar surface. (d) Combined image of the lymphatic and blood vessel network. Scale bars: 500 µm.

Fig. 6
Fig. 6

Longitudinal lymphatic and blood vessel imaging of a scar on Patient 2. (a)-(c) Minimum projection image of OCT signal (from 200 to 300 µm below skin surface) at time points C, D and E with the corresponding lymphatic vessel images in (d)-(f) (animations in Visualization 2, Visualization 3, and Visualization 4) and combined lymphatic and blood vessel images in (g)-(i). Arrows indicate the common vessel patterns. All images are 6 × 4.5 mm. Scale bars: 500 µm.

Fig. 7
Fig. 7

Longitudinal quantification of lymphatic vessel area density.

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

D(x,y,z)=1 m=1 M n=1 N [(i(x+m,y,z+n,t) i(x,y,z,t) ¯ )(i(x+m,y,z+n,t') i(x,y,z,t') ¯ )] m=1 M n=1 N (i(x+m,y,z+n,t) i(x,y,z,t) ¯ ) 2 m=1 M n=1 N (i(x+m,y,z+n,t') i(x,y,z,t') ¯ ) 2 ,.
i 2 (z)F(z)S(z)ρ e 2 μ t z ,
i 0 2 (z)F(z)S(z) ρ 0 e 2 μ t0 z ,
I corrected =ln[ i 2 (z) i 0 2 (z) ]=2( μ t μ t0 )z+ln( ρ ρ 0 )+a,
I'(z)= I corrected +2( μ t μ t0 )z.

Metrics