Abstract

We have proposed a tested in tissue phantoms and in vivo a novel sensor based on optical coherence tomography (OCT) for noninvasive and continuous monitoring of blood glucose concentration. OCT images were obtained from pig and rabbit skin before and after glucose administration. Slopes of OCT signals decreased substantially (40% in tissues in vivo) and linearly with the increase of blood glucose concentration from 4 to 30  mM, typical for normal and diabetic subjects. Phantom studies demonstrated 1% accuracy of scattering-coefficient measurement. Our theoretical and experimental studies suggest that glucose concentration can potentially be measured noninvasively with high sensitivity and accuracy with OCT systems.

© 2001 Optical Society of America

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References

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1997 (2)

G. L. Cote, J. Clin. Eng. 22, 253 (1997).
[CrossRef]

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

1996 (1)

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

1994 (2)

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

1986 (1)

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Beall, P.

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Bohren, C. F.

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

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Chumakov, Yu. P.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Cope, M.

Cote, G. L.

G. L. Cote, J. Clin. Eng. 22, 253 (1997).
[CrossRef]

Denisendo, A. N.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Duck, F. A.

F. A. Duck, Physical Properties of Tissue (Academic, London, 1990).

Fantini, S.

Feisullin, S.

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Feldchtein, F. I.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Franceschini, M. A.

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Gelikonov, G. V.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Gelikonov, V. M.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Gladkova, N. D.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Gratton, E.

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, Science 254, 1178 (1991).
[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, Science 254, 1178 (1991).
[CrossRef] [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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Huffman, D. R.

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

Kohl, M.

Kon, I.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

Kuranov, R. V.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Kurihara-Berhstrom, T.

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Kuznetzone, I. A.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Maier, J. S.

Maksimova, I.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

Mavlutov, A.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

Mishin, A.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

Pochinko, V. V.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Sergeev, A. M.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Shakhov, A. V.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Shakhova, N. M.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Snopova, L. B.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Strelzova, O. S.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Tuchin, V. V.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

Van de Hulst, H. C.

H. C. Van de Hulst, Light Scattering by Small Particles (Dover, New York, 1981).

Walker, S. A.

Woodworth, M.

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Zimnyakov, D.

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

J. Clin. Eng. (1)

G. L. Cote, J. Clin. Eng. 22, 253 (1997).
[CrossRef]

Lab. Anin. Sci. (1)

T. Kurihara-Berhstrom, M. Woodworth, S. Feisullin, and P. Beall, Lab. Anin. Sci. 36, 396 (1986).

Opt. Exp. (1)

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzone, A. N. Denisendo, V. V. Pochinko, Yu. P. Chumakov, and O. S. Strelzova, Opt. Exp. 1, 432 (1997), http://www.opticsexpress.org .
[CrossRef]

Opt. Lett. (2)

Proc. SPIE (1)

V. V. Tuchin, I. Maksimova, D. Zimnyakov, I. Kon, A. Mavlutov, and A. Mishin, Proc. SPIE 2925, 118 (1996).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef] [PubMed]

Other (6)

National Institute of Diabetes and Digestive and Kidney Diseases, Vol. 94 of Diabetes Overview (National Institutes of Health, Bethesda, Md., 1994).

H. C. Van de Hulst, Light Scattering by Small Particles (Dover, New York, 1981).

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

C. Lentner, ed., Geigy Scientific Tables (Ciba-Geigy, Basel, Switzerland, 1984), p. 69.

R. C. Weast, ed., CRC Handbook of Chemistry and Physics, 70th ed. (CRC, Cleveland, Ohio, 1989).

F. A. Duck, Physical Properties of Tissue (Academic, London, 1990).

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Figures (4)

Fig. 1
Fig. 1

Slope of OCT signal mean±standard deviation and scattering coefficient (line) as a function of glucose concentration in the aqueous solution of polystyrene microspheres.

Fig. 2
Fig. 2

Inverted slope of OCT signals (recorded from rabbit ears) and blood glucose concentration measured at different times after bolus glucose injections.

Fig. 3
Fig. 3

Inverted slope of OCT signals (recorded from Yucatan pig skin) and blood glucose concentration measured at different times during glucose clamping experiments (for clarity, not all data points are shown).

Fig. 4
Fig. 4

Slope of OCT signals (recorded from Yucatan pig skin) as a function of blood glucose concentration and scattering efficiency calculated by Mie theory.

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