Abstract

Contrast agents are utilized in virtually every imaging modality to enhance diagnostic capabilities. We introduce a novel class of optical contrast agent, namely, encapsulating microspheres, that are based not on fluorescence but on scattering nanoparticles within the shell or core. The agents are suitable for reflection- or scattering-based techniques such as optical coherence tomography, light microscopy, and reflectance confocal microscopy. We characterize the optical properties of gold-, melanin-, and carbon-shelled contrast agents and demonstrate enhancement of optical coherence tomography imaging after intravenous injection of such an agent into a mouse.

© 2003 Optical Society of America

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[CrossRef] [PubMed]

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M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

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A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Achilefu, S.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, J. Biomed. Opt. 6, 122 (2001).
[CrossRef] [PubMed]

Anderson, R. R.

A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

Bacon, E. R.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Barton, J. K.

J. K. Barton, J. B. Hoying, and C. J. Sullivan, Acad. Radiol. 9S, 52 (2002).
[CrossRef]

Boppart, S. A.

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, Opt. Lett. 27, 2010 (2002).
[CrossRef]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Bouma, B. E.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Brezinski, M. E.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Bugaj, J. E.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, J. Biomed. Opt. 6, 122 (2001).
[CrossRef] [PubMed]

Christiansen, C.

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

Cooper, E. R.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Dorshow, R. B.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, J. Biomed. Opt. 6, 122 (2001).
[CrossRef] [PubMed]

Fujimoto, J. G.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Fuller, K. A.

Gazelle, G. S.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Grinstaff, M. W.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Halpern, E. F.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Hoying, J. B.

J. K. Barton, J. B. Hoying, and C. J. Sullivan, Acad. Radiol. 9S, 52 (2002).
[CrossRef]

Jacques, S. L.

Jiang, J.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Kozikowski, S. D.

S. K. Kurtz, S. D. Kozikowski, and L. J. Wolfram, in Electro-Optics and Photorefractive Materials, P. Gunther, ed. (Springer-Verlag, Berlin, 1986), p. 110.

Kryvi, H.

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

Kurtz, S. K.

S. K. Kurtz, S. D. Kozikowski, and L. J. Wolfram, in Electro-Optics and Photorefractive Materials, P. Gunther, ed. (Springer-Verlag, Berlin, 1986), p. 110.

Lao, X.

M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

Liu, K. J.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Marks, D. L.

McIntire, G. L.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Muhler, A.

M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

Nalcioglu, O.

M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

Oldenburg, A. L.

Pitris, C.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Rajagopalan, R.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, J. Biomed. Opt. 6, 122 (2001).
[CrossRef] [PubMed]

Reynolds, J. J.

Skotland, T.

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

Sontum, P. C.

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

Southern, J. F.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Su, M. Y.

M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

Sullivan, C. J.

J. K. Barton, J. B. Hoying, and C. J. Sullivan, Acad. Radiol. 9S, 52 (2002).
[CrossRef]

Suslick, K. S.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Swartz, H. M.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Torner, J. L.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Vitkin, A.

A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

Wang, L.

Wang, W.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Wilson, B. C.

A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

Wolf, G. L.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

Wolfram, L. J.

S. K. Kurtz, S. D. Kozikowski, and L. J. Wolfram, in Electro-Optics and Photorefractive Materials, P. Gunther, ed. (Springer-Verlag, Berlin, 1986), p. 110.

Woolsey, J.

A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

Acad. Radiol.

G. S. Gazelle, G. L. Wolf, G. L. McIntire, E. R. Bacon, E. F. Halpern, E. R. Cooper, and J. L. Torner, Acad. Radiol. 1, 373 (1994).
[CrossRef] [PubMed]

J. K. Barton, J. B. Hoying, and C. J. Sullivan, Acad. Radiol. 9S, 52 (2002).
[CrossRef]

Appl. Opt.

Biophys. J.

K. J. Liu, M. W. Grinstaff, J. Jiang, K. S. Suslick, H. M. Swartz, and W. Wang, Biophys. J. 67, 896 (1994).
[CrossRef] [PubMed]

Biotechnol. Appl. Biochem.

C. Christiansen, H. Kryvi, P. C. Sontum, and T. Skotland, Biotechnol. Appl. Biochem. 19, 307 (1994).

J. Biomed. Opt.

J. E. Bugaj, S. Achilefu, R. B. Dorshow, and R. Rajagopalan, J. Biomed. Opt. 6, 122 (2001).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

Magn. Reson. Med.

M. Y. Su, A. Muhler, X. Lao, and O. Nalcioglu, Magn. Reson. Med. 39, 259 (1998).
[CrossRef] [PubMed]

Nature Med.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, Nature Med. 4, 861 (1998).
[CrossRef]

Opt. Lett.

Photochem. Photobiol.

A. Vitkin, J. Woolsey, B. C. Wilson, and R. R. Anderson, Photochem. Photobiol. 59, 455 (1994).
[CrossRef] [PubMed]

Other

S. K. Kurtz, S. D. Kozikowski, and L. J. Wolfram, in Electro-Optics and Photorefractive Materials, P. Gunther, ed. (Springer-Verlag, Berlin, 1986), p. 110.

B. E. Bouma and G. J. Tearney, eds., Handbook of Optical Coherence Tomography (Marcel Dekker, New York, 2001).
[CrossRef]

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Figures (2)

Fig. 1
Fig. 1

Scanning- (left) and transmission- (right) electron micrographs of an oil-filled microsphere contrast agent, showing scattering silica nanoparticles in the shell.

Fig. 2
Fig. 2

OCT image enhancement with contrast agents. Images of mouse liver (left) without and (right) with gold-shelled oil-filled microsphere contrast agents.

Tables (1)

Tables Icon

Table 1 Optical Properties of OCT Contrast Agentsa

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