Abstract

A method for noninvasively detecting hemoglobin oxygen saturation (SO2) and carboxyhemoglobin saturation (SCO) in subcutaneous microvasculature with multiwavelength photoacoustic microscopy is presented. Blood samples mixed with different concentrations of carboxyhemoglobin were used to test the feasibility and accuracy of photoacoustic microscopy compared with the blood-gas analyzer. Moreover, fixed-point detection of SO2 and SCO in mouse ear was obtained, and the changes from normoxia to carbon monoxide hypoxia were dynamically monitored in vivo. Experimental results demonstrate that multiwavelength photoacoustic microscopy can detect SO2 and SCO, which has future potential clinical applications.

© 2012 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
    [CrossRef]
  2. D. Malonek and A. Grinvad, Science 272, 551 (1996).
    [CrossRef]
  3. A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
    [CrossRef]
  4. E. M. Dwyer and G. M. Turino, N. Engl. J. Med. 321, 1474 (1989).
    [CrossRef]
  5. E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
    [CrossRef]
  6. H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
    [CrossRef]
  7. K. Maslov, G. Stoica, and L. V. Wang, Opt. Lett. 30, 625 (2005).
    [CrossRef]
  8. Y. Yuan, S. H. Yang, and D. Xing, Appl. Phys. Lett. 100, 023702 (2012).
    [CrossRef]
  9. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
    [CrossRef]
  10. I. Y. Petrov, Y. Petrov, D. S. Prough, D. J. Deyo, I. Cicenaite, and R. O. Esenaliev, Biomed. Opt. Express 3, 125 (2012).
    [CrossRef]
  11. H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
    [CrossRef]
  12. Y. Wang, S. Hu, K. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, Opt. Lett. 36, 1029 (2011).
    [CrossRef]
  13. T. Jetzfellner, A. Rosenthal, A. Buehler, K. Englmeier, D. Razansky, and V. Ntziachristos, Opt. Lett. 36, 4176 (2011).
    [CrossRef]
  14. B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
    [CrossRef]
  15. J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
    [CrossRef]
  16. R. Ma, A. Taruttis, V. Ntziachristos, and D. Razansky, Opt. Express 17, 21414 (2009).
    [CrossRef]
  17. G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
    [CrossRef]
  18. J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
    [CrossRef]

2012

2011

2009

R. Ma, A. Taruttis, V. Ntziachristos, and D. Razansky, Opt. Express 17, 21414 (2009).
[CrossRef]

G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
[CrossRef]

2007

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

2006

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

2005

2003

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
[CrossRef]

1999

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

1996

D. Malonek and A. Grinvad, Science 272, 551 (1996).
[CrossRef]

1991

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

1989

E. M. Dwyer and G. M. Turino, N. Engl. J. Med. 321, 1474 (1989).
[CrossRef]

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

1988

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Allred, E. N.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Balakrishnan, G.

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

Beard, P.

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

Bleecker, E. R.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Borer, E.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Buehler, A.

Chaitman, B. R.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Chance, B.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Cicenaite, I.

Dahms, T. E.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Delpy, D.

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

Deyo, D. J.

Dwyer, E. M.

E. M. Dwyer and G. M. Turino, N. Engl. J. Med. 321, 1474 (1989).
[CrossRef]

Elwell, C.

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

Englmeier, K.

Esenaliev, R. O.

Evans, A.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Fromm, R. E.

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

Goetting, M. G.

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

Gottlieb, S. O.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Grinvad, A.

D. Malonek and A. Grinvad, Science 272, 551 (1996).
[CrossRef]

Gueler, A.

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

Hackney, J. D.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Holtom, G.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Hu, S.

Intaglietta, M.

A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
[CrossRef]

Jetzfellner, T.

Johnson, P. C.

A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
[CrossRef]

Kent, J.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Ku, G.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Laufer, J.

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

Ma, R.

Malonek, D.

D. Malonek and A. Grinvad, Science 272, 551 (1996).
[CrossRef]

Marik, P. E.

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

Maris, M.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Maslov, K.

Y. Wang, S. Hu, K. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, Opt. Lett. 36, 1029 (2011).
[CrossRef]

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

K. Maslov, G. Stoica, and L. V. Wang, Opt. Lett. 30, 625 (2005).
[CrossRef]

McCormick, P. W.

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

Mccully, K.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Northrop, J.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Ntziachristos, V.

Pagano, M.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Pang, Y.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Petrov, I. Y.

Petrov, Y.

Prough, D. S.

Razansky, D.

Rosenthal, A.

Selvester, R. H.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Shinkwin, M.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Sivaramakrishnan, M.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

Stewart, M.

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

Stoica, G.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

K. Maslov, G. Stoica, and L. V. Wang, Opt. Lett. 30, 625 (2005).
[CrossRef]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Taruttis, A.

Tsai, A. G.

A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
[CrossRef]

Turino, G. M.

E. M. Dwyer and G. M. Turino, N. Engl. J. Med. 321, 1474 (1989).
[CrossRef]

Varon, J.

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

Walden, S. M.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Wang, L. V.

Y. Wang, S. Hu, K. Maslov, Y. Zhang, Y. Xia, and L. V. Wang, Opt. Lett. 36, 1029 (2011).
[CrossRef]

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

K. Maslov, G. Stoica, and L. V. Wang, Opt. Lett. 30, 625 (2005).
[CrossRef]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Wang, X.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Wang, Y.

Warren, J.

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Xia, Y.

Xie, X.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Xing, D.

Y. Yuan, S. H. Yang, and D. Xing, Appl. Phys. Lett. 100, 023702 (2012).
[CrossRef]

G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
[CrossRef]

Yang, S. H.

Y. Yuan, S. H. Yang, and D. Xing, Appl. Phys. Lett. 100, 023702 (2012).
[CrossRef]

G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
[CrossRef]

Yin, G. Z.

G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
[CrossRef]

Yuan, Y.

Y. Yuan, S. H. Yang, and D. Xing, Appl. Phys. Lett. 100, 023702 (2012).
[CrossRef]

Zhang, H. F.

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

Zhang, Y.

Ann. N.Y. Acad. Sci.

B. Chance, E. Borer, A. Evans, G. Holtom, J. Kent, M. Maris, K. Mccully, J. Northrop, and M. Shinkwin, Ann. N.Y. Acad. Sci. 551, 1 (1988).
[CrossRef]

Appl. Phys. Lett.

Y. Yuan, S. H. Yang, and D. Xing, Appl. Phys. Lett. 100, 023702 (2012).
[CrossRef]

H. F. Zhang, K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang, Appl. Phys. Lett. 90, 053901 (2007).
[CrossRef]

Biomed. Opt. Express

J. Appl. Phys.

G. Z. Yin, D. Xing, and S. H. Yang, J. Appl. Phys. 106, 013109 (2009).
[CrossRef]

J. Emerg. Med.

J. Varon, P. E. Marik, R. E. Fromm, and A. Gueler, J. Emerg. Med. 17, 87 (1999).
[CrossRef]

N. Engl. J. Med.

E. M. Dwyer and G. M. Turino, N. Engl. J. Med. 321, 1474 (1989).
[CrossRef]

E. N. Allred, E. R. Bleecker, B. R. Chaitman, T. E. Dahms, S. O. Gottlieb, J. D. Hackney, M. Pagano, R. H. Selvester, S. M. Walden, and J. Warren, N. Engl. J. Med. 321, 1426 (1989).
[CrossRef]

Nat. Biotechnol.

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24, 848 (2006).
[CrossRef]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef]

Opt. Express

Opt. Lett.

Physiol. Rev.

A. G. Tsai, P. C. Johnson, and M. Intaglietta, Physiol. Rev. 83, 933 (2003).
[CrossRef]

Proc. SPIE

J. Laufer, C. Elwell, D. Delpy, and P. Beard, Proc. SPIE 6086, 60861J (2006).
[CrossRef]

Science

D. Malonek and A. Grinvad, Science 272, 551 (1996).
[CrossRef]

Stroke

P. W. McCormick, M. Stewart, M. G. Goetting, and G. Balakrishnan, Stroke 22, 596 (1991).
[CrossRef]

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (4)

Fig. 1.
Fig. 1.

Scheme of the in vivo PAM system. The diameter of the pinhole is 100 μm.

Fig. 2.
Fig. 2.

(a) Absorption spectra of the three hemoglobin species: Hb, HbO2, and HbCO; (b) The PA signals of in vitro blood sample at 70.54% SO2 and 28.1% SCO level. Comparison of the PAM measurements with the blood-gas analyzer measurements of (c) SCO and (d) SO2 in vitro mouse blood samples.

Fig. 3.
Fig. 3.

(a) PAM image of microvasculature in a mouse ear at the wavelength of 532 nm under normoxia. The lateral resolution is 50μm; (b) The reconstructed profile of the blood vessel obtained at 760, 850, and 900 nm, respectively, at the position indicated by the dashed line in (a). PA measured; (c) SCO; and (d) SO2 levels of the vein and artery vessels at the position indicated by the dashed line in (a). SD, standard deviation; U, uncertainty.

Fig. 4.
Fig. 4.

PAM monitoring of (a) SCO and (b) SO2 level changes in vein and artery of mouse ear from normoxia to carbon monoxide hypoxia.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

μa(λi)=εHb(λi)[Hb]+εHbO2(λi)[HbO2]+εHbCO(λi)[HbCO],
[[Hb][HbO2][HbCO]](r)=E1P(r)K,
P(r)=[p(λ1,r)p(λn,r)],E=[εHb(λ1)εHbO2(λ1)εHbCO(λ1)εHb(λn)εHbO2(λn)εHbCO(λn)].
SO2=[HbO2][Hb]+[HbO2]+[HbCO],SCO=[HbCO][Hb]+[HbO2]+[HbCO].

Metrics