Abstract

Holographic optical coherence imaging is a full-frame variant of coherence-domain imaging. An optoelectronic semiconductor holographic film functions as a coherence filter placed before a conventional digital video camera that passes coherent (structure-bearing) light to the camera during holographic readout while preferentially rejecting scattered light. The data are acquired as a succession of en face images at increasing depth inside the sample in a fly-through acquisition. The samples of living tissue were rat osteogenic sarcoma multicellular tumor spheroids that were grown from a single osteoblast cell line in a bioreactor. Tumor spheroids are nearly spherical and have radial symmetry, presenting a simple geometry for analysis. The tumors investigated ranged in diameter from several hundred micrometers to over 1 mm. Holographic features from the tumors were observed in reflection to depths of 500–600 μm with a total tissue path length of approximately 14 mean free paths. The volumetric data from the tumor spheroids reveal heterogeneous structure, presumably caused by necrosis and microcalcifications characteristic of some human avascular tumors.

© 2004 Optical Society of America

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2004

2003

P. Yu, M. Mustata, P. M. W. French, J. J. Turek, M. R. Melloch, D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
[CrossRef]

2002

L. Vabre, A. Dubois, A. C. Boccara, “Thermal-light full-field optical coherence tomography,” Opt. Lett. 27, 530–532 (2002).
[CrossRef]

M. Laubscher, M. Ducros, B. Karamata, T. Lasser, R. Salathe, “Video-rate three-dimensional optical coherence tomography,” Opt. Exp. 10, 429–435 (2002), http://www.opticsexpress.org .
[CrossRef]

2001

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med. 7, 502–507 (2001).
[CrossRef] [PubMed]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

S. Bourquin, P. Seitz, R. P. Salathe, “Optical coherence topography based on a two-dimensional smart detector array,” Opt. Lett. 26, 512–514 (2001).
[CrossRef]

D. D. Nolte, T. Cubel, L. J. Pyrak-Nolte, M. R. Melloch, “Adaptive beam combining and interferometry with photorefractive quantum wells,” J. Opt. Soc. Am. B. 18, 195–205 (2001).
[CrossRef]

1999

D. D. Nolte, “Semi-insulating semiconductor heterostructures: optoelectronic properties and applications,” J. Appl. Phys. 85, 6259 (1999).
[CrossRef]

Y. Ding, A. M. Weiner, M. R. Melloch, D. D. Nolte, “Adaptive all-order dispersion compensation of ultrafast laser pulses using dynamic spectral holography,” Appl. Phys. Lett. 75, 3255–3257 (1999).
[CrossRef]

A. G. Podoleanu, J. A. Rogers, D. A. Jackson, “OCT en-face images from the retina with adjustable depth resolution in real time,” IEEE J. Sel. Top. Quantum Electron. 5, 1176–1184 (1999).
[CrossRef]

1998

R. Jones, M. Tziraki, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic 3-D imaging using photorefractive multiple quantum well devices,” Opt. Exp. 2, 439–448 (1998), http://www.opticsexpress.org .
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

L. A. Kunz-Schughart, M. Kreutz, R. Knuechel, “Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology,” Int. J. Exp. Pathol. 79, 1–23 (1998).
[CrossRef] [PubMed]

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
[CrossRef]

Y. Ding, D. D. Nolte, M. R. Melloch, A. M. Weiner, “Time-domain image processing using dynamic holography,” IEEE J. Sel. Top. Quantum Electron. 4, 332–341 (1998).
[CrossRef]

R. Hamamoto, K. Yamada, M. Kamihira, S. Iijima, “Differentiation and proliferation of primary rat hepatocytes cultured as spheroids,” J. Biochem. (Tokyo) 124, 972–979 (1998).
[CrossRef]

G. Hamilton, “Multicellular spheroids as an in vitro tumor model,” Cancer Lett. 131, 29–34 (1998).
[CrossRef] [PubMed]

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

E. Beaurepaire, A. C. Boccara, M. Lebec, L. Blanchot, H. Saint-Jalmes, “Full-field optical coherence microscopy,” Opt. Lett. 23, 244–246 (1998).
[CrossRef]

J. M. Schmitt, S. H. Xiang, “Cross-polarized backscatter in optical coherence tomography of biological tissue,” Opt. Lett. 23, 1060–1062 (1998).
[CrossRef]

1997

L. de Ridder, “Autologous confrontation of brain tumor-derived spheroids with human dermal spheroids,” Anticancer Res. 17, 4119–4120 (1997).

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, A. J. Welch, “Optical coherence tomography for biodiagnostics,” Opt. Photon. News 8, 41–47 (1997).
[CrossRef]

Y. Ding, R. M. Brubaker, D. D. Nolte, M. R. Melloch, A. M. Weiner, “Femtosecond pulse shaping by dynamic holograms in photorefractive multiple quantum wells,” Opt. Lett. 22, 718–720 (1997).
[CrossRef] [PubMed]

1996

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, M. V. Sivak, “Optical coherence tomography and microscopy in gastrointenstinal tissues,” IEEE J. Sel. Top. Quantum Electron. 2, 1017–1028 (1996).
[CrossRef]

K. Groebe, W. Mueller-Klieser, “On the relation between size of necrosis and diameter of tumor spheroids,” Int. J. Radiat. Oncol. Biol. Phys. 34, 395–401 (1996).
[CrossRef] [PubMed]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

P. Hargrave, P. W. Nicholson, D. T. Delpy, M. Firbank, “Optical properties of multicellular tumour spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef] [PubMed]

1995

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
[CrossRef] [PubMed]

1992

1991

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

1990

1989

N. H. Abramson, K. G. Spears, “Single pulse light-in-flight recording by holography,” Appl. Opt. 28, 1834–1841 (1989).
[CrossRef] [PubMed]

K. G. Spears, J. Serafin, N. H. Abramson, X. Zhu, H. Bjelkhagen, “Chrono-coherent imaging for medicine,” IEEE Trans. Biomed. Eng. 36, 1210–1214 (1989).
[CrossRef] [PubMed]

1978

A. W. Lohmann, C. A. Schmalfuss, “Holography through fog: a new version,” Opt. Commun. 26, 318–321 (1978).
[CrossRef]

1971

1967

1965

H. Kogelnik, “Holographic image projection through inhomogeneous media,” Bell Syst. Tech. J. 44, 2451–2455 (1965).
[CrossRef]

Abramson, N. H.

N. H. Abramson, K. G. Spears, “Single pulse light-in-flight recording by holography,” Appl. Opt. 28, 1834–1841 (1989).
[CrossRef] [PubMed]

K. G. Spears, J. Serafin, N. H. Abramson, X. Zhu, H. Bjelkhagen, “Chrono-coherent imaging for medicine,” IEEE Trans. Biomed. Eng. 36, 1210–1214 (1989).
[CrossRef] [PubMed]

Ansari, Z.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Bacher, G. D.

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
[CrossRef]

Barry, N. P.

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

Barton, J. K.

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, A. J. Welch, “Optical coherence tomography for biodiagnostics,” Opt. Photon. News 8, 41–47 (1997).
[CrossRef]

Beaurepaire, E.

Bjelkhagen, H.

K. G. Spears, J. Serafin, N. H. Abramson, X. Zhu, H. Bjelkhagen, “Chrono-coherent imaging for medicine,” IEEE Trans. Biomed. Eng. 36, 1210–1214 (1989).
[CrossRef] [PubMed]

Blanchot, L.

Boccara, A. C.

Boppart, S. A.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
[CrossRef] [PubMed]

Bouma, B.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
[CrossRef] [PubMed]

Bourquin, S.

Brezinski, M. E.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
[CrossRef] [PubMed]

Brubaker, R. M.

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

Cubel, T.

D. D. Nolte, T. Cubel, L. J. Pyrak-Nolte, M. R. Melloch, “Adaptive beam combining and interferometry with photorefractive quantum wells,” J. Opt. Soc. Am. B. 18, 195–205 (2001).
[CrossRef]

Dainty, J. C.

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

de Ridder, L.

L. de Ridder, “Autologous confrontation of brain tumor-derived spheroids with human dermal spheroids,” Anticancer Res. 17, 4119–4120 (1997).

Delpy, D. T.

P. Hargrave, P. W. Nicholson, D. T. Delpy, M. Firbank, “Optical properties of multicellular tumour spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef] [PubMed]

Ding, Y.

Y. Ding, A. M. Weiner, M. R. Melloch, D. D. Nolte, “Adaptive all-order dispersion compensation of ultrafast laser pulses using dynamic spectral holography,” Appl. Phys. Lett. 75, 3255–3257 (1999).
[CrossRef]

Y. Ding, D. D. Nolte, M. R. Melloch, A. M. Weiner, “Time-domain image processing using dynamic holography,” IEEE J. Sel. Top. Quantum Electron. 4, 332–341 (1998).
[CrossRef]

Y. Ding, R. M. Brubaker, D. D. Nolte, M. R. Melloch, A. M. Weiner, “Femtosecond pulse shaping by dynamic holograms in photorefractive multiple quantum wells,” Opt. Lett. 22, 718–720 (1997).
[CrossRef] [PubMed]

Doran, G. E.

Drexler, W.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med. 7, 502–507 (2001).
[CrossRef] [PubMed]

Dubois, A.

Ducros, M.

M. Laubscher, M. Ducros, B. Karamata, T. Lasser, R. Salathe, “Video-rate three-dimensional optical coherence tomography,” Opt. Exp. 10, 429–435 (2002), http://www.opticsexpress.org .
[CrossRef]

Duguay, M. A.

Dunsby, C. W.

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Firbank, M.

P. Hargrave, P. W. Nicholson, D. T. Delpy, M. Firbank, “Optical properties of multicellular tumour spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef] [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. Puliafto, J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef] [PubMed]

French, P. M. W.

P. Yu, M. Mustata, P. M. W. French, J. J. Turek, M. R. Melloch, D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
[CrossRef]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

R. Jones, M. Tziraki, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic 3-D imaging using photorefractive multiple quantum well devices,” Opt. Exp. 2, 439–448 (1998), http://www.opticsexpress.org .
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

P. Yu, M. Mustata, W. Headley, D. D. Nolte, J. J. Turek, P. M. W. French, “Optical coherence imaging of rat tumor spheroids,” in Coherence Domain Optical Methods in Biomedical Science and Clinical Applications VI, V. V. Tuchin, J. A. Izatt, J. G. Fujomoto, eds., Proc. SPIE4619, 210–218 (2002).
[CrossRef]

Fujimoto, J. G.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med. 7, 502–507 (2001).
[CrossRef] [PubMed]

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
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M. R. Hee, D. Huang, E. A. Swanson, J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992).
[CrossRef]

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

Ghanta, R. K.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med. 7, 502–507 (2001).
[CrossRef] [PubMed]

Glass, A. M.

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

Groebe, K.

K. Groebe, W. Mueller-Klieser, “On the relation between size of necrosis and diameter of tumor spheroids,” Int. J. Radiat. Oncol. Biol. Phys. 34, 395–401 (1996).
[CrossRef] [PubMed]

Gu, Y.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Hamamoto, R.

R. Hamamoto, K. Yamada, M. Kamihira, S. Iijima, “Differentiation and proliferation of primary rat hepatocytes cultured as spheroids,” J. Biochem. (Tokyo) 124, 972–979 (1998).
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Hamilton, G.

G. Hamilton, “Multicellular spheroids as an in vitro tumor model,” Cancer Lett. 131, 29–34 (1998).
[CrossRef] [PubMed]

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P. Hargrave, P. W. Nicholson, D. T. Delpy, M. Firbank, “Optical properties of multicellular tumour spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef] [PubMed]

Headley, W.

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

P. Yu, M. Mustata, W. Headley, D. D. Nolte, J. J. Turek, P. M. W. French, “Optical coherence imaging of rat tumor spheroids,” in Coherence Domain Optical Methods in Biomedical Science and Clinical Applications VI, V. V. Tuchin, J. A. Izatt, J. G. Fujomoto, eds., Proc. SPIE4619, 210–218 (2002).
[CrossRef]

Hee, M. R.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
[CrossRef] [PubMed]

M. R. Hee, D. Huang, E. A. Swanson, J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992).
[CrossRef]

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

Huang, D.

M. R. Hee, D. Huang, E. A. Swanson, J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging,” J. Opt. Soc. Am. B 9, 903–908 (1992).
[CrossRef]

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

Hyde, S. C. W.

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

Iijima, S.

R. Hamamoto, K. Yamada, M. Kamihira, S. Iijima, “Differentiation and proliferation of primary rat hepatocytes cultured as spheroids,” J. Biochem. (Tokyo) 124, 972–979 (1998).
[CrossRef]

Itoh, M.

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Izatt, J. A.

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, A. J. Welch, “Optical coherence tomography for biodiagnostics,” Opt. Photon. News 8, 41–47 (1997).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, M. V. Sivak, “Optical coherence tomography and microscopy in gastrointenstinal tissues,” IEEE J. Sel. Top. Quantum Electron. 2, 1017–1028 (1996).
[CrossRef]

Jackson, D. A.

A. G. Podoleanu, J. A. Rogers, D. A. Jackson, “OCT en-face images from the retina with adjustable depth resolution in real time,” IEEE J. Sel. Top. Quantum Electron. 5, 1176–1184 (1999).
[CrossRef]

Jones, R.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

R. Jones, M. Tziraki, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic 3-D imaging using photorefractive multiple quantum well devices,” Opt. Exp. 2, 439–448 (1998), http://www.opticsexpress.org .
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

Kamihira, M.

R. Hamamoto, K. Yamada, M. Kamihira, S. Iijima, “Differentiation and proliferation of primary rat hepatocytes cultured as spheroids,” J. Biochem. (Tokyo) 124, 972–979 (1998).
[CrossRef]

Karamata, B.

M. Laubscher, M. Ducros, B. Karamata, T. Lasser, R. Salathe, “Video-rate three-dimensional optical coherence tomography,” Opt. Exp. 10, 429–435 (2002), http://www.opticsexpress.org .
[CrossRef]

Kartner, F. X.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med. 7, 502–507 (2001).
[CrossRef] [PubMed]

Klein, M. B.

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
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Knox, W. H.

Knuechel, R.

L. A. Kunz-Schughart, M. Kreutz, R. Knuechel, “Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology,” Int. J. Exp. Pathol. 79, 1–23 (1998).
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Kobayashi, K.

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, A. J. Welch, “Optical coherence tomography for biodiagnostics,” Opt. Photon. News 8, 41–47 (1997).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, M. V. Sivak, “Optical coherence tomography and microscopy in gastrointenstinal tissues,” IEEE J. Sel. Top. Quantum Electron. 2, 1017–1028 (1996).
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L. A. Kunz-Schughart, M. Kreutz, R. Knuechel, “Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology,” Int. J. Exp. Pathol. 79, 1–23 (1998).
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Kruger, R. A.

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
[CrossRef]

Kulkarni, M. D.

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, A. J. Welch, “Optical coherence tomography for biodiagnostics,” Opt. Photon. News 8, 41–47 (1997).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, M. V. Sivak, “Optical coherence tomography and microscopy in gastrointenstinal tissues,” IEEE J. Sel. Top. Quantum Electron. 2, 1017–1028 (1996).
[CrossRef]

Kunz-Schughart, L. A.

L. A. Kunz-Schughart, M. Kreutz, R. Knuechel, “Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology,” Int. J. Exp. Pathol. 79, 1–23 (1998).
[CrossRef] [PubMed]

Kwolek, K. M.

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

R. Jones, M. Tziraki, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic 3-D imaging using photorefractive multiple quantum well devices,” Opt. Exp. 2, 439–448 (1998), http://www.opticsexpress.org .
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R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
[CrossRef]

R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
[CrossRef]

S. C. W. Hyde, R. Jones, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Depth-resolved holography through turbid media using photorefraction,” IEEE J. Sel. Top. Quantum Electron. 2, 965–975 (1996).
[CrossRef]

Lahiri, I.

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
[CrossRef]

Lasser, T.

M. Laubscher, M. Ducros, B. Karamata, T. Lasser, R. Salathe, “Video-rate three-dimensional optical coherence tomography,” Opt. Exp. 10, 429–435 (2002), http://www.opticsexpress.org .
[CrossRef]

Laubscher, M.

M. Laubscher, M. Ducros, B. Karamata, T. Lasser, R. Salathe, “Video-rate three-dimensional optical coherence tomography,” Opt. Exp. 10, 429–435 (2002), http://www.opticsexpress.org .
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Lebec, M.

Leith, E. N.

E. N. Leith, J. Upatnieks, “Holograms: their properties and uses,” in Geometric Optics I, H. R. Stoppach, ed., Proc. SPIE4, 3–6 (1965).

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. Puliafto, J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
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A. W. Lohmann, C. A. Schmalfuss, “Holography through fog: a new version,” Opt. Commun. 26, 318–321 (1978).
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R. Jones, S. C. W. Hyde, M. J. Lynn, N. P. Barry, J. C. Dainty, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Holographic storage and high background imaging using photorefractive multiple quantum wells,” Appl. Phys. Lett. 69, 1837–1839 (1996).
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Mattick, A. T.

Melloch, M. R.

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29, 68–70 (2004).
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P. Yu, M. Mustata, P. M. W. French, J. J. Turek, M. R. Melloch, D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
[CrossRef]

Z. Ansari, Y. Gu, J. Siegel, D. Parsons-Karavassilis, C. W. Dunsby, M. Itoh, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, W. Headley, M. R. Melloch, “High-frame-rate, 3-D photorefractive holography through turbid media with arbitrary sources and photorefractive structured illumination,” IEEE J Sel. Top. Quantum Electron. 7, 878–886 (2001).
[CrossRef]

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett. 26, 334–336 (2001).
[CrossRef]

D. D. Nolte, T. Cubel, L. J. Pyrak-Nolte, M. R. Melloch, “Adaptive beam combining and interferometry with photorefractive quantum wells,” J. Opt. Soc. Am. B. 18, 195–205 (2001).
[CrossRef]

Y. Ding, A. M. Weiner, M. R. Melloch, D. D. Nolte, “Adaptive all-order dispersion compensation of ultrafast laser pulses using dynamic spectral holography,” Appl. Phys. Lett. 75, 3255–3257 (1999).
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, M. Tziraki, J. C. Dainty, P. M. W. French, D. D. Nolte, K. M. Kwolek, M. R. Melloch, “Real-time 3-D holographic imaging using photorefractive media including multiple-quantum-well devices,” IEEE J. Sel. Top. Quantum Electron. 4, 360–369 (1998).
[CrossRef]

Y. Ding, D. D. Nolte, M. R. Melloch, A. M. Weiner, “Time-domain image processing using dynamic holography,” IEEE J. Sel. Top. Quantum Electron. 4, 332–341 (1998).
[CrossRef]

I. Lahiri, L. J. Pyrak-Nolte, D. D. Nolte, M. R. Melloch, R. A. Kruger, G. D. Bacher, M. B. Klein, “Laser-based ultrasound detection using photorefractive quantum wells,” Appl. Phys. Lett. 73, 1041–1043 (1998).
[CrossRef]

R. Jones, M. Tziraki, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic 3-D imaging using photorefractive multiple quantum well devices,” Opt. Exp. 2, 439–448 (1998), http://www.opticsexpress.org .
[CrossRef]

R. Jones, N. P. Barry, S. C. W. Hyde, P. M. W. French, K. M. Kwolek, D. D. Nolte, M. R. Melloch, “Direct-to-video holographic readout in quantum wells for three-dimensional imaging through turbid media,” Opt. Lett. 23, 103–105 (1998).
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P. Yu, M. Mustata, P. M. W. French, J. J. Turek, M. R. Melloch, D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
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Figures (15)

Fig. 1
Fig. 1

Principle of holographic coherence gating in a PRQW film. The film responds only to the gradient in intensity rather than to the intensity itself. This allows the weak holographic fringes to be recorded while the high-intensity diffuse light passes through. In the degenerate four-wave mixing geometry, the reference is also the readout, diffracting from the film into the camera. This approach is direct imaging with the hologram acting as a coherence filter that depth gates coherent backscattered light from the diffuse specimen.

Fig. 2
Fig. 2

Simulation of holography as spatial heterodyne. (a) The image speckle from the diffuse object is spatially modulated through interference with the reference by a carrier wave with a spatial carrier frequency 1/Λ. (b) The spatial spectrum of the image (dotted curve) and hologram (solid curve) shows the strong sidebands in the hologram that rejects the zero order by many orders of magnitude. DR, dynamic range.

Fig. 3
Fig. 3

Holographic OCI experimental layout. (a) The general layout shows the illumination source and the modified Mach-Zehnder interferometer in a degenerate four-wave mixing configuration. The sample is interrogated in reflection and the polarization is selected by the polarizing beam splitter (BS). A key element in the reference arm is the piezomirror that vibrates at a rate that is tracked by the holographic film, but not by the camera, thereby time averaging the parasitic cross talk (non-image-bearing) speckle. (b) Shows the details of the Fourier optics used to filter the optical images. The hologram is recorded in an image plane. ND, neutral density filter.

Fig. 4
Fig. 4

Postacquisition image processing. (a) The background-subtracted holographic X,Y section of tumor T0508A-03 with a diameter of 600 μm that is 200 μm deep inside the tumor. (b) The same section after Fourier filtering along the z axis to remove the remaining background.

Fig. 5
Fig. 5

(a) Transmission low-magnification microscope image of a 700-μm-diameter tumor spheroid. (b) Conventional scanning electron micrograph of a different 700-μm tumor spheroid showing individual cells on the surface. (c) Optical thin-section micrographs of a 900-μm-diameter tumor spheroid, showing a thin outermost shell of healthy cells approximately 100 μm thick, with innercore necroses and microcalcifications. (d) Enlargement of the rectangular section showing details of the healthy shell and the inner necroses.

Fig. 6
Fig. 6

Selected X,Y (en face) sections of a 600-μm-diameter tumor (T0508A-03). The fly-through has 200 frames with a depth step of 7.4 μm (in the tumor). Only every fifth section is shown. The top of the tumor is at frame 68, and the Petri dish reflection is at frame 150. The medial cross section is at frame 108.

Fig. 7
Fig. 7

Reconstructed Y,Z sections (B scans) through the same spheroid and data volume of Fig. 6. The aspect-ratio is not 1:1, showing the tumor as elliptical. The Petri dish reflection is on the right of each frame, and the illumination is from the left. The medial cross section is frame 100.

Fig. 8
Fig. 8

Selected views of the 600-μm-diameter tumor spheroid of Figs. 6 and 7. (a) Medial cross section presented as a Y,Z B scan. Note the size and shape of the shadow on the back of the tumor and on the Petri dish reflection. (b) Integrated view produced by summation of the data volume along the x axis. This is equivalent to transillumination data. (c) Medial en face cross section at a depth of 300 μm from the top of the tumor.

Fig. 9
Fig. 9

Medial X,Y sections of five different tumors of increasing size. Each image is autoscaled separately (the small tumor presents the weakest hologram, whereas the strongest holograms come from the 1-mm-diameter tumor).

Fig. 10
Fig. 10

Comparison between OCT and holographic OCI data sets. These are medial cross sections of different tumors. The OCT system was a rapid-scan system operating at a 1.3-μm-wavelength (courtesy of A. Rollins, Case Western University). The superior spatial resolution and signal-to-noise ratio of the OCT B scan is evident, but the OCI image is a single section of a data volume. The spatial resolution difference is not fundamental, and improvements in OCI should approach the spatial resolution of OCT. Improvements in holographic film quality will improve sensitivity and the signal-to-noise ratio.

Fig. 11
Fig. 11

Three-dimensional volumetric reconstruction of a 640-μm-diameter of a multicellular tumor spheroid showing the shadow on the Petri dish and the internal holographic features of the necrotic core.

Fig. 12
Fig. 12

Average autocorrelation analysis of the X,Y images of a fly-through with line plots of the autocorrelation peak, showing lateral resolution of approximately 50 μm and longitudinal resolution of 30 μm.

Fig. 13
Fig. 13

Consecutive fly-through X,Y pseudotransillumination cross sections of a cross-linked tumor (top) and a healthy tumor (bottom). The holographic features in the cross-linked tumor are highly repeatable. In the healthy tumor, some features are persistent, but most are not. The dynamic nature of the healthy tumor arises from cellular motility and can be used as an index of cellular health.

Fig. 14
Fig. 14

Cross correlations of the consecutive fly-throughs of Fig. 13. The cross-linked tumor shows an autocorrelation peak of 90%, whereas the healthy tumor (with dynamic speckle) shows a correlation of only 60% relative to a random 50% cross correlation between two dissimilar tumors.

Fig. 15
Fig. 15

Intensity dependence of the holographic features as a function of radius from the center for three tumors of different size. The small tumor shows the weakest holograms and the largest tumor shows the the strongest holograms. All show a general decrease of average intensity toward the rim of the tumor. These results agree statistically with histology performed on separate tumors.

Equations (2)

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Λ=λ2 sin θ,
AT=y0 ln1+A/y0,

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