Abstract

Scattering limits the penetration depth of most optical imaging techniques. Efforts to overcome this limitation often require complex optical or computational schemes. We have developed a new method of assessing tissue properties based on spectroscopic analysis of multiply scattered light. The technique, multispectral multiple-scattering low-coherence interferometry (ms2/LCI), uses coherence and spatial gating to produce images of tissue optical properties up to 9 mm deep, with millimeter-scale resolution. The capabilities of ms2/LCI are demonstrated using tissue phantoms composed of chicken breast. Discrimination of diseased and healthy tissues is shown through imaging and analysis of burns in ex vivo human skin samples. Our technique may provide a powerful way to assess burn depth and progression in sensitive, burned tissues where physical contact is undesirable.

© 2014 Optical Society of America

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References

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2013 (3)

2012 (1)

2011 (4)

M. G. Giacomelli, A. Wax, “Imaging beyond the ballistic limit in coherence imaging using multiply scattered light,” Opt. Express 19, 4268–4279 (2011).
[Crossref]

X. Xu, H. Liu, L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5, 154–157 (2011).
[Crossref]

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

F. E. Robles, C. Wilson, G. Grant, A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5, 744–747 (2011).
[Crossref]

2010 (6)

2009 (4)

F. Robles, R. N. Graf, A. Wax, “Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution,” Opt. Express 17, 6799–6812 (2009).
[Crossref]

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem. 19, 6407–6411 (2009).
[Crossref]

E. M. Hillman, S. A. Burgess, “Sub-millimeter resolution 3D optical imaging of living tissue using laminar optical tomography,” Laser Photon. Rev. 3, 159–179 (2009).

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3, 503–509 (2009).
[Crossref]

2008 (4)

R. F. Spaide, H. Koizumi, M. C. Pozonni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146, 496–500 (2008).

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

C.-W. Lu, C.-K. Lee, M.-T. Tsai, Y.-M. Wang, C. C. Yang, “Measurement of the hemoglobin oxygen saturation level with spectroscopic spectral-domain optical coherence tomography,” Opt. Lett. 33, 416–418 (2008).
[Crossref]

S. A. Burgess, M. B. Bouchard, B. Yuan, E. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett. 33, 2710–2712 (2008).
[Crossref]

2006 (2)

C. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, S. A. Boppart, “Spectroscopic spectral-domain optical coherence microscopy,” Opt. Lett. 31, 1079–1081 (2006).
[Crossref]

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

2005 (1)

2004 (2)

2000 (2)

1998 (1)

1993 (2)

1990 (1)

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[Crossref]

Alfano, R. R.

Applegate, B.

Applegate, B. E.

Boppart, S. A.

Bouchard, M. B.

Brown, W. J.

Burgess, S. A.

E. M. Hillman, S. A. Burgess, “Sub-millimeter resolution 3D optical imaging of living tissue using laminar optical tomography,” Laser Photon. Rev. 3, 159–179 (2009).

S. A. Burgess, M. B. Bouchard, B. Yuan, E. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett. 33, 2710–2712 (2008).
[Crossref]

Cancio, L. C.

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

Cang, H.

Chen, J.

Cheong, W. F.

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[Crossref]

Choma, M. A.

Chowdhury, S.

Clark, R. A.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

Coolen, N. A.

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

Corso, P. S.

E. Finkelstein, P. S. Corso, T. R. Miller, The Incidence and Economic Burden of Injuries in the United States (Oxford University, 2006).

Crawford, L.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

Das, B. B.

Drexler, W.

Dunn, A. K.

Eckert, J.

Fercher, A. F.

Finkelstein, E.

E. Finkelstein, P. S. Corso, T. R. Miller, The Incidence and Economic Burden of Injuries in the United States (Oxford University, 2006).

Fleming, C. P.

Fujimoto, J. G.

Gardecki, J. A.

Giacomelli, M. G.

Graf, R. N.

Grant, G.

F. E. Robles, C. Wilson, G. Grant, A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5, 744–747 (2011).
[Crossref]

Halpern, E. F.

Hansen, M. N.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem. 19, 6407–6411 (2009).
[Crossref]

Hee, M. R.

Hillman, E.

Hillman, E. M.

E. M. Hillman, S. A. Burgess, “Sub-millimeter resolution 3D optical imaging of living tissue using laminar optical tomography,” Laser Photon. Rev. 3, 159–179 (2009).

Hirth, D.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

Hitzenberger, C. K.

Holcomb, J. B.

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

Horstmeyer, R.

B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7, 300–305 (2013).
[Crossref]

Ippen, E. P.

Izatt, J. A.

Jacob, D.

Jacobson, J. M.

Jaskille, A. D.

A. D. Jaskille, J. C. Ramella-Roman, J. W. Shupp, M. H. Jordan, J. C. Jeng, “Critical review of burn depth assessment techniques: part II. Review of laser doppler technology,” J. Burn Care Res. 31, 151–157 (2010).

Jeng, J. C.

A. D. Jaskille, J. C. Ramella-Roman, J. W. Shupp, M. H. Jordan, J. C. Jeng, “Critical review of burn depth assessment techniques: part II. Review of laser doppler technology,” J. Burn Care Res. 31, 151–157 (2010).

Jordan, M. H.

A. D. Jaskille, J. C. Ramella-Roman, J. W. Shupp, M. H. Jordan, J. C. Jeng, “Critical review of burn depth assessment techniques: part II. Review of laser doppler technology,” J. Burn Care Res. 31, 151–157 (2010).

Judkewitz, B.

B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7, 300–305 (2013).
[Crossref]

Kärtner, F. X.

Kauvar, D. S.

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

Koizumi, H.

R. F. Spaide, H. Koizumi, M. C. Pozonni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146, 496–500 (2008).

Kowalczyk, A.

Lee, C.-K.

Lee, J.

Leitgeb, R.

Li, X.

Li, X. D.

Li, Y. L.

Li, Z.-Y.

Lin, F.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

Liu, H.

X. Xu, H. Liu, L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5, 154–157 (2011).
[Crossref]

Lu, C.-W.

Luo, W.

Marks, D. L.

Mathy, A.

B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7, 300–305 (2013).
[Crossref]

Matthews, T. E.

McClain, S. A.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

McGuckin, L. E. L.

Middelkoop, E.

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

Miller, T. R.

E. Finkelstein, P. S. Corso, T. R. Miller, The Incidence and Economic Burden of Injuries in the United States (Oxford University, 2006).

Morgner, U.

Oldenburg, A. L.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem. 19, 6407–6411 (2009).
[Crossref]

Pitris, C.

Pozonni, M. C.

R. F. Spaide, H. Koizumi, M. C. Pozonni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146, 496–500 (2008).

Prahl, S. A.

W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[Crossref]

Ralston, T. S.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem. 19, 6407–6411 (2009).
[Crossref]

C. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, S. A. Boppart, “Spectroscopic spectral-domain optical coherence microscopy,” Opt. Lett. 31, 1079–1081 (2006).
[Crossref]

Ramella-Roman, J. C.

A. D. Jaskille, J. C. Ramella-Roman, J. W. Shupp, M. H. Jordan, J. C. Jeng, “Critical review of burn depth assessment techniques: part II. Review of laser doppler technology,” J. Burn Care Res. 31, 151–157 (2010).

Renz, E. M.

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

Richards-Kortum, R.

Robles, F.

Robles, F. E.

Seekell, K.

Sharma, S.

Shelton, R. L.

Shupp, J. W.

A. D. Jaskille, J. C. Ramella-Roman, J. W. Shupp, M. H. Jordan, J. C. Jeng, “Critical review of burn depth assessment techniques: part II. Review of laser doppler technology,” J. Burn Care Res. 31, 151–157 (2010).

Simon, J. D.

Singer, A. J.

A. J. Singer, D. Hirth, S. A. McClain, L. Crawford, F. Lin, R. A. Clark, “Validation of a vertical progression porcine burn model,” J. Burn Care Res. 32, 638–646 (2011).

Smithpeter, C. L.

Spaide, R. F.

R. F. Spaide, H. Koizumi, M. C. Pozonni, “Enhanced depth imaging spectral-domain optical coherence tomography,” Am. J. Ophthalmol. 146, 496–500 (2008).

Sticker, M.

Sun, T.

Swanson, E. A.

Tan, W.

Tearney, G. J.

Tsai, M.-T.

Tuchin, V.

V. V. Tuchin, V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis (SPIE, 2007), Vol. PM166.

Tuchin, V. V.

V. V. Tuchin, V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis (SPIE, 2007), Vol. PM166.

Ulrich, M. M.

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

Van Den Bogaerdt, A. J.

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

Vinegoni, C.

Vlig, M.

N. A. Coolen, M. Vlig, A. J. Van Den Bogaerdt, E. Middelkoop, M. M. Ulrich, “Development of an in vitro burn wound model,” Wound Repair Regen. 16, 559–567 (2008).

Wade, C. E.

D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
[Crossref]

Wang, L. V.

X. Xu, H. Liu, L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5, 154–157 (2011).
[Crossref]

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3, 503–509 (2009).
[Crossref]

Wang, Y. M.

B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7, 300–305 (2013).
[Crossref]

Wang, Y.-M.

Wax, A.

T. E. Matthews, M. G. Giacomelli, W. J. Brown, A. Wax, “Fourier domain multispectral multiple scattering low coherence interferometry,” Appl. Opt. 52, 8220–8228 (2013).
[Crossref]

Y. L. Li, K. Seekell, H. Yuan, F. E. Robles, A. Wax, “Multispectral nanoparticle contrast agents for true-color spectroscopic optical coherence tomography,” Biomed. Opt. Express 3, 1914–1923 (2012).
[Crossref]

F. E. Robles, C. Wilson, G. Grant, A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics 5, 744–747 (2011).
[Crossref]

M. G. Giacomelli, A. Wax, “Imaging beyond the ballistic limit in coherence imaging using multiply scattered light,” Opt. Express 19, 4268–4279 (2011).
[Crossref]

F. E. Robles, S. Chowdhury, A. Wax, “Assessing hemoglobin concentration using spectroscopic optical coherence tomography for feasibility of tissue diagnostics,” Biomed. Opt. Express 1, 310–317 (2010).
[Crossref]

F. E. Robles, Y. Zhu, J. Lee, S. Sharma, A. Wax, “Detection of early colorectal cancer development in the azoxymethane rat carcinogenesis model with Fourier domain low coherence interferometry,” Biomed. Opt. Express 1, 736–745 (2010).
[Crossref]

F. E. Robles, A. Wax, “Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry,” Opt. Lett. 35, 360–362 (2010).
[Crossref]

F. E. Robles, A. Wax, “Separating the scattering and absorption coefficients using the real and imaginary parts of the refractive index with low-coherence interferometry,” Opt. Lett. 35, 2843–2845 (2010).
[Crossref]

F. Robles, R. N. Graf, A. Wax, “Dual window method for processing spectroscopic optical coherence tomography signals with simultaneously high spectral and temporal resolution,” Opt. Express 17, 6799–6812 (2009).
[Crossref]

Wei, A.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem. 19, 6407–6411 (2009).
[Crossref]

Welch, A. J.

C. L. Smithpeter, A. K. Dunn, A. J. Welch, R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” Appl. Opt. 37, 2749–2754 (1998).
[Crossref]

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D. S. Kauvar, S. E. Wolf, C. E. Wade, L. C. Cancio, E. M. Renz, J. B. Holcomb, “Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns),” Burns 32, 853–857 (2006).
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Figures (8)

Fig. 1.
Fig. 1.

Diagram of ms2/LCI scheme, including detail of focal zone and example photon path.

Fig. 2.
Fig. 2.

Imaging geometry for chicken breast experiments.

Fig. 3.
Fig. 3.

Top: ms2/LCI imaging of a mirror sample through up to 8.8 mm thick chicken breast. The depth range of the technique is 5.6 mm, so two data acquisitions at different depths are shown here. The red arrow shows the surface of chicken breast, and the white arrow shows the complex conjugate artifact of a strong signal from the mirror that is seen below. Bottom: Depth profiles from the lower image showing depth profiles at 0, 6, and 13 mm lateral positions.

Fig. 4.
Fig. 4.

Top: ms2/LCI imaging of chicken breast phantom with spectroscopic contrast. False coloring provided by mapping the spectral content to the provided color scheme appears in the bottom right panel. The chicken breast surface is evident at the top, while the tendon is visible at the bottom. The schematic on the bottom left shows the physical arrangement of the phantom components. Spectroscopic contrast reveals the presence of a dye-filled capillary by the apparent color shift. Detailed examination of the spectra (see Fig. 5) shows the dye absorption and that of the region of interest (ROI).

Fig. 5.
Fig. 5.

Spectral detail for image in Fig. 4. (a) Recovered absoprtion spectrum of dye as compared to a reference measurement, (b) absorption spectrum of ROI compared to those of oxyhemoglobin and methemoglobin.

Fig. 6.
Fig. 6.

Intensity-only ms2/LCI imaging of burned ex vivo human skin. (a) Deep second- degree burn created by applying a brass rod heated to 100°C for 30 s, (b) shallow second-degree burn created by applying a brass rod heated to 80°C for 20 s. Both examples show decreased scattering associated with the burned section compared to the unburned section in both the epidermis, the topmost 1 mm of the tissue, and the dermis, at deeper layers. The contrast is less apparent in the shallow second-degree burn.

Fig. 7.
Fig. 7.

False coloring of ms2/LCI images of burned ex vivo human tissues. (a) Intensity-only image of a deep second-degree burn (right) compared to unburned tissue (left). The epidermal layer shows changes in the signal at the surface, with a more organized structure at the surface of the unburned than the burned tissue. (b) False colored ms2/LCI image based on spectral content between 620 and 700 nm (same color scheme as in Fig. 4), (c) histological image of the same burned tissue at 10× magnification; (d) raw spectral data taken at the base of the dermis [dotted lines in (b)] show clear changes between the burned and unburned tissue. The increased signal intensity at lower wavelengths agrees with physiological changes due to burn.

Fig. 8.
Fig. 8.

ms/LCI imaging of burned ex vivo human tissues. (a) False colored ms2/LCI image of a superficial first-degree burn (right) compared to unburned tissue (left), with the same color scheme as in Fig. 4. Little change is seen in signal intensity or spectral content. (b) Histological image of the same burned tissue at 10× magnification; (c) the raw spectra from the base of the dermis [dotted lines in (a)] show no changes between burned and unburned tissue.

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