Abstract

Cellular resolution imaging of biological structures has always been a challenge due to strong scattering that limits the achievable transverse resolution or imaging penetration depth. Recently, a major advancement toward high-resolution and volumetric imaging was achieved by implementing a parallel detection (i.e., full field) into Fourier-domain optical coherence tomography. The drawback of using parallel detection is that scattered light can travel laterally and get mapped improperly at a camera creating optical crosstalk, which severely impairs the interpretation of subcellular images and limits its use in medical diagnostics. In this work, we demonstrate for what we believe is the first time how to efficiently reduce crosstalk and enable microscopic quality volumetric reconstructions of the scattering tissue-like human skin in vivo, all within less than a half of a second. To minimize crosstalk, we implemented a very fast deformable membrane that introduces random phase illumination. Additionally, the sample is illuminated under variable angles to reduce the contrast of speckles by incoherent summation of the crosstalk-free volumes. Introducing crosstalk and speckle-free OCT will advance imaging prospects closer to the ideal of a noninvasive optical biopsy.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2019 (2)

2018 (3)

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

H. Spahr, C. Pfaffle, P. Koch, H. Sudkamp, G. Huttmann, and D. Hillmann, “Interferometric detection of 3D motion using computational subapertures in optical coherence tomography,” Opt. Express 26, 18803–18816 (2018).
[Crossref]

F. Shevlin, “Phase randomization for spatiotemporal averaging of unwanted interference effects arising from coherence,” Appl. Opt. 57, E6–E10 (2018).
[Crossref]

2017 (5)

2016 (3)

2015 (2)

A. Federici and A. Dubois, “Full-field optical coherence microscopy with optimized ultrahigh spatial resolution,” Opt. Lett. 40, 5347–5350 (2015).
[Crossref]

N. D. Shemonski, F. A. South, Y. Z. Liu, S. G. Adie, P. S. Carney, and S. A. Boppart, “Computational high-resolution optical imaging of the living human retina,” Nat. Photonics 9, 440–443 (2015).
[Crossref]

2014 (3)

2013 (1)

2012 (2)

2011 (1)

2010 (1)

M. Wojtkowski, “High-speed optical coherence tomography: basics and applications,” Appl. Opt. 49, D30–61 (2010).
[Crossref]

2009 (1)

H. Wang and A. M. Rollins, “Speckle reduction in optical coherence tomography using angular compounding by B-scan Doppler-shift encoding,” J. Biomed. Opt. 14, 030512 (2009).
[Crossref]

2008 (2)

S. N. Lashansky, S. Mansbach, M. J. Berger, T. Karasik, and M. Bin-Nun, “Edge response revisited,” Proc. SPIE 6941, 69410Z (2008).
[Crossref]

D. D. Duncan, S. J. Kirkpatrick, and R. K. K. Wang, “Statistics of local speckle contrast,” J. Opt. Soc. Am. A 25, 9–15 (2008).
[Crossref]

2007 (3)

A. F. Fercher, “Medical optics—Perspectives,” Z. Med. Phys. 17, 1–2 (2007).
[Crossref]

A. E. Desjardins, B. J. Vakoc, W. Y. Oh, S. M. Motaghiannezam, G. J. Tearney, and B. E. Bouma, “Angle-resolved optical coherence tomography with sequential angular selectivity for speckle reduction,” Opt. Express 15, 6200–6209 (2007).
[Crossref]

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, “Interferometric synthetic aperture microscopy,” Nat. Phys. 3, 129–134 (2007).
[Crossref]

2006 (2)

2005 (3)

2004 (2)

2003 (1)

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8, 260–263 (2003).
[Crossref]

2002 (2)

2000 (2)

M. G. Somekh, C. W. See, and J. Goh, “Wide field amplitude and phase confocal microscope with speckle illumination,” Opt. Commun. 174, 75–80 (2000).
[Crossref]

M. Bashkansky and J. Reintjes, “Statistics and reduction of speckle in optical coherence tomography,” Opt. Lett. 25, 545–547 (2000).
[Crossref]

1999 (2)

J. M. Schmitt, S. H. Xiang, and K. M. Yung, “Speckle in optical coherence tomography,” J. Biomed. Opt. 4, 95–105 (1999).
[Crossref]

J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205–1215 (1999).
[Crossref]

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, 1178–1181 (1991).
[Crossref]

1976 (1)

Aalders, M. C. G.

Abdulhalim, I.

Adie, S. G.

N. D. Shemonski, F. A. South, Y. Z. Liu, S. G. Adie, P. S. Carney, and S. A. Boppart, “Computational high-resolution optical imaging of the living human retina,” Nat. Photonics 9, 440–443 (2015).
[Crossref]

Arthaber, H.

Auksorius, E.

E. Auksorius and A. C. Boccara, “Fast subsurface fingerprint imaging with full-field optical coherence tomography system equipped with a silicon camera,” J. Biomed. Opt. 22, 1–8 (2017).
[Crossref]

Azimani, H.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

Barut, A.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

Bashkansky, M.

Beaurepaire, E.

Berger, M. J.

S. N. Lashansky, S. Mansbach, M. J. Berger, T. Karasik, and M. Bin-Nun, “Edge response revisited,” Proc. SPIE 6941, 69410Z (2008).
[Crossref]

Bian, Y.

Bin-Nun, M.

S. N. Lashansky, S. Mansbach, M. J. Berger, T. Karasik, and M. Bin-Nun, “Edge response revisited,” Proc. SPIE 6941, 69410Z (2008).
[Crossref]

Boccara, A. C.

E. Auksorius and A. C. Boccara, “Fast subsurface fingerprint imaging with full-field optical coherence tomography system equipped with a silicon camera,” J. Biomed. Opt. 22, 1–8 (2017).
[Crossref]

Boccara, A.-C.

Boppart, S. A.

N. D. Shemonski, F. A. South, Y. Z. Liu, S. G. Adie, P. S. Carney, and S. A. Boppart, “Computational high-resolution optical imaging of the living human retina,” Nat. Photonics 9, 440–443 (2015).
[Crossref]

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, “Interferometric synthetic aperture microscopy,” Nat. Phys. 3, 129–134 (2007).
[Crossref]

Borycki, D.

Bouma, B. E.

Bourquin, S.

Bromberg, Y.

Cao, H.

Carney, P. S.

N. D. Shemonski, F. A. South, Y. Z. Liu, S. G. Adie, P. S. Carney, and S. A. Boppart, “Computational high-resolution optical imaging of the living human retina,” Nat. Photonics 9, 440–443 (2015).
[Crossref]

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, “Interferometric synthetic aperture microscopy,” Nat. Phys. 3, 129–134 (2007).
[Crossref]

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, 1178–1181 (1991).
[Crossref]

Choi, W.

Choi, Y.

Choma, M.

Choma, M. A.

B. Redding, Y. Bromberg, M. A. Choma, and H. Cao, “Full-field interferometric confocal microscopy using a VCSEL array,” Opt. Lett. 39, 4446–4449 (2014).
[Crossref]

B. Redding, M. A. Choma, and H. Cao, “Speckle-free laser imaging using random laser illumination,” Nat. Photonics 6, 355–359 (2012).
[Crossref]

Cinotti, E.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

Dasari, R. R.

Del Marmol, V.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

Desjardins, A. E.

Drexler, W.

Dubois, A.

J. Ogien and A. Dubois, “A compact high-speed full-field optical coherence microscope for high-resolution in vivo skin imaging,” J. Biophoton. 12, e201800208 (2019).
[Crossref]

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

J. Ogien and A. Dubois, “High-resolution full-field optical coherence microscopy using a broadband light-emitting diode,” Opt. Express 24, 9922–9931 (2016).
[Crossref]

A. Federici and A. Dubois, “Full-field optical coherence microscopy with optimized ultrahigh spatial resolution,” Opt. Lett. 40, 5347–5350 (2015).
[Crossref]

A. Dubois, L. Vabre, A.-C. Boccara, and E. Beaurepaire, “High-resolution full-field optical coherence tomography with a Linnik microscope,” Appl. Opt. 41, 805–812 (2002).
[Crossref]

Duncan, D. D.

Faber, D. J.

Federici, A.

Fercher, A. F.

A. F. Fercher, “Medical optics—Perspectives,” Z. Med. Phys. 17, 1–2 (2007).
[Crossref]

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, 1178–1181 (1991).
[Crossref]

Franke, G.

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, 1178–1181 (1991).
[Crossref]

Ginner, L.

Goh, J.

M. G. Somekh, C. W. See, and J. Goh, “Wide field amplitude and phase confocal microscope with speckle illumination,” Opt. Commun. 174, 75–80 (2000).
[Crossref]

Goodman, J. W.

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, 1178–1181 (1991).
[Crossref]

Hain, C.

Hamkalo, M.

Hassler, K.

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, 1178–1181 (1991).
[Crossref]

Hermann, B.

Hillmann, D.

Hinkel, L.

Hosseini, P.

Huang, B. K.

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, 1178–1181 (1991).
[Crossref]

Huttmann, G.

Iftimia, N.

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by “path length encoded” angular compounding,” J. Biomed. Opt. 8, 260–263 (2003).
[Crossref]

Jin, D.

Karamata, B.

Karasik, T.

S. N. Lashansky, S. Mansbach, M. J. Berger, T. Karasik, and M. Bin-Nun, “Edge response revisited,” Proc. SPIE 6941, 69410Z (2008).
[Crossref]

Khokha, M. K.

Kim, Y. H.

Kirkpatrick, S. J.

Koch, P.

Kozaki, H.

Kuang, C.

Kumar, A.

Lambelet, P.

Lashansky, S. N.

S. N. Lashansky, S. Mansbach, M. J. Berger, T. Karasik, and M. Bin-Nun, “Edge response revisited,” Proc. SPIE 6941, 69410Z (2008).
[Crossref]

Lasser, T.

Laubscher, M.

Lee, K. J.

Leitgeb, R. A.

Leutenegger, M.

Levecq, O.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
[Crossref]

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, 1178–1181 (1991).
[Crossref]

Liu, Y. Z.

N. D. Shemonski, F. A. South, Y. Z. Liu, S. G. Adie, P. S. Carney, and S. A. Boppart, “Computational high-resolution optical imaging of the living human retina,” Nat. Photonics 9, 440–443 (2015).
[Crossref]

Malvehy, J.

A. Dubois, O. Levecq, H. Azimani, D. Siret, A. Barut, M. Suppa, V. Del Marmol, J. Malvehy, E. Cinotti, P. Rubegni, and J. L. Perrot, “Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors,” J. Biomed. Opt. 23, 1–9(2018).
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Mansbach, S.

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Supplementary Material (4)

NameDescription
» Supplement 1       Supplemental document.
» Visualization 1       Fly through 3-D cross-noise free Fd-FF-OCT reconstruction of human forearm skin in vivo in XY planes
» Visualization 2       Fly through 3-D cross-noise free Fd-FF-OCT reconstruction of human forearm skin in vivo in XZ planes
» Visualization 3       Fly through 3-D cross-noise free Fd-FF-OCT reconstruction of human forearm skin in vivo in YZ planes

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Figures (7)

Fig. 1.
Fig. 1. Principle of crosstalk-free FD-FF-OCT: (a) Multiply scattered light can be rejected by using a pinhole placed in the front of the photodetector—the solution used in scanning OCT devices; (b) Origin of the crosstalk: Full-field OCT with spatially coherent illumination uses numerous detection channels, hence the multiply scattered light contributes to interference in pixels that are improperly mapped with respect to the real image of the measured object; (c) Crosstalk-free FF-OCT: The spatial phase modulation introduced by the deformable membrane (DM) placed in front of the interferometer washes out fringes originating from multiply scattered light, effectively reducing the crosstalk.
Fig. 2.
Fig. 2. Scheme of the FD-FF-OCT setup capable of crosstalk and speckle noise suppression: L1–L8, achromatic doublet lenses; G, galvo scanner introducing additional angular compounding; MO1 and MO2, 10× Olympus objectives with 0.3NA; RM, reference mirror; BS, beam splitter.
Fig. 3.
Fig. 3. (a) Interferometric fringe visibility as a function of defocus recorded at three defocus values (300μm, 0 μm, and 800 μm) with DM in inactive (top) and active (bottom) states. (b) Fringe visibility curves estimated as a function of defocus when DM is in the active (red) and inactive (green) states. Decrease of resolution as a function of defocus is shown for comparison purpose (blue dots). Pink bar corresponds to the theoretical value of the DOF. (c) Phase decorrelation as a function of defocus recorded at three defocus values (300μm, 0 μm, and 800 μm) with DM in active state.
Fig. 4.
Fig. 4. Crosstalk and speckle removal using random phase illumination (RandPhase) and angular compounding (AngComp): (a) cross-sectional images parallel to the direction of light propagation -optical B-scans; (b) cross-sectional images in the plane transverse to the direction of light at a depth of 500 μm below the surface of the phantom; and (c), (d) derivative of the spatial distribution of the backscattered signal intensity calculated along the yellow dashed lines marked on images (a) and (b).
Fig. 5.
Fig. 5. Comparison of scanning OCT and crosstalk-free FD-FF-OCT systems performed on 3D scattering phantom: (a) cross-sectional image (optical B scans) measured by scanning OCT (YZ plane), (b) crosstalk-free FD-FF-OCT cross-sectional image; (c), (d) XY cross-sectional images corresponding to the axial planes indicated by red lines; and (e) LSFs calculated along yellow dashed lines marked in panels (a), (b). Yellow boxes indicate areas used to calculate the speckle contrast K.
Fig. 6.
Fig. 6. Crosstalk-free FD-FF-OCT in vivo images of human forearm skin: (a) data visualized in linear scale for XZ and YZ cross-sections (optical B scans); red arrow indicates probable localization of individual melanocytes in the stratum spinosum; yellow arrow shows granular structure corresponding to cells in the stratum spinosum; green arrow indicates sebaceous glands in the dermis in proximity of a hair follicle; and (b) representative cross-sectional image displayed in logarithmic greyscale. Data used for full volumetric reconstruction (512×512×512pixels) were acquired within 0.4 s (36 volumes).
Fig. 7.
Fig. 7. Crosstalk-free FD-FF-OCT images of human forearm skin in vivo: XY cross-sections corresponding to various axial planes; Δz indicates the depth below the surface of skin.