Abstract

Optical techniques for in vivo measurement of blood flow velocity are not quite applicable for determination of velocity of individual cells or nanoparticles. Here, we describe a photoacoustic time-of-flight method to measure the velocity of individual absorbing objects by using single and multiple laser beams. Its capability was demonstrated in vitro on blood vessel phantom and in vivo on an animal (mouse) model for estimating velocity of gold nanorods, melanin nanoparticles, erythrocytes, leukocytes, and circulating tumor cells in the broad range of flow velocity from 0.1mm/s to 14cm/s. Object velocity can be used to identify single cells circulating at different velocities or cell aggregates and to determine a cell’s location in a vessel cross-section.

© 2011 Optical Society of America

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  1. Y. Yeh and H. Z. Cummins, Appl. Phys. Lett. 4, 176 (1964).
    [CrossRef]
  2. H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
    [CrossRef] [PubMed]
  3. J.A.Sell, ed., Photothermal Investigations of Solids and Fluids (Academic, New York, 1989).
  4. V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).
  5. V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
    [CrossRef] [PubMed]
  6. E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
    [CrossRef] [PubMed]
  7. D. A. Nedosekin, M. Sarimollaoglu, E. V. Shashkov, E. I. Galanzha, and V. P. Zharov, Opt. Express 18, 8605(2010).
    [CrossRef] [PubMed]
  8. S. E. Charm and G. S. Kurland, Blood Flow and MicroCirculation (Wiley, New York, 1974).
  9. M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
    [PubMed]

2010

2009

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

2007

H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
[CrossRef] [PubMed]

2005

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
[CrossRef] [PubMed]

2004

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).

1988

M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
[PubMed]

1964

Y. Yeh and H. Z. Cummins, Appl. Phys. Lett. 4, 176 (1964).
[CrossRef]

Charm, S. E.

S. E. Charm and G. S. Kurland, Blood Flow and MicroCirculation (Wiley, New York, 1974).

Cummins, H. Z.

Y. Yeh and H. Z. Cummins, Appl. Phys. Lett. 4, 176 (1964).
[CrossRef]

Fang, H.

H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
[CrossRef] [PubMed]

Fernandez, B.

M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
[PubMed]

Galanzha, E. I.

D. A. Nedosekin, M. Sarimollaoglu, E. V. Shashkov, E. I. Galanzha, and V. P. Zharov, Opt. Express 18, 8605(2010).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).

Ishikawa, M.

M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
[PubMed]

Kerbel, R. S.

M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
[PubMed]

Kurland, G. S.

S. E. Charm and G. S. Kurland, Blood Flow and MicroCirculation (Wiley, New York, 1974).

Maslov, K.

H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
[CrossRef] [PubMed]

Nedosekin, D. A.

Sarimollaoglu, M.

Shashkov, E. V.

D. A. Nedosekin, M. Sarimollaoglu, E. V. Shashkov, E. I. Galanzha, and V. P. Zharov, Opt. Express 18, 8605(2010).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

Spring, P. M.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

Suen, J. Y.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

Tuchin, V. V.

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).

Wang, L. V.

H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
[CrossRef] [PubMed]

Yeh, Y.

Y. Yeh and H. Z. Cummins, Appl. Phys. Lett. 4, 176 (1964).
[CrossRef]

Zharov, V. P.

D. A. Nedosekin, M. Sarimollaoglu, E. V. Shashkov, E. I. Galanzha, and V. P. Zharov, Opt. Express 18, 8605(2010).
[CrossRef] [PubMed]

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
[CrossRef] [PubMed]

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).

Appl. Phys. Lett.

Y. Yeh and H. Z. Cummins, Appl. Phys. Lett. 4, 176 (1964).
[CrossRef]

Cancer Res.

E. I. Galanzha, E. V. Shashkov, P. M. Spring, J. Y. Suen, and V. P. Zharov, Cancer Res. 69, 7926 (2009).
[CrossRef] [PubMed]

M. Ishikawa, B. Fernandez, and R. S. Kerbel, Cancer Res. 48, 4897 (1988).
[PubMed]

J Biomed Opt.

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, J Biomed Opt. 10, 051502 (2005).
[CrossRef] [PubMed]

Opt. Express

Phys. Rev. Lett.

H. Fang, K. Maslov, and L. V. Wang, Phys. Rev. Lett. 99, 184501 (2007).
[CrossRef] [PubMed]

Proc. SPIE

V. P. Zharov, E. I. Galanzha, and V. V. Tuchin, Proc. SPIE 5320, 256 (2004).

Other

J.A.Sell, ed., Photothermal Investigations of Solids and Fluids (Academic, New York, 1989).

S. E. Charm and G. S. Kurland, Blood Flow and MicroCirculation (Wiley, New York, 1974).

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Figures (4)

Fig. 1
Fig. 1

(a) PA time-of-flight velocity measurement with cylindrical laser beam. (b) Shapes of PA peaks for different sized objects (illustrated on the left as red or brown circles) and various beam geometries (one- or three-beam; illustrated as green ovals).

Fig. 2
Fig. 2

In vitro time-of-flight PAFC. (a) Suspension of B16F10 cells; scale bar, 50 μm . (b) Calculated (line) and experimentally obtained (diamonds) peak widths for one-beam PAFC ( 1064 nm laser). (c) Melanin suspension in 300 μm capillary tube with three-diode laser beam PAFC ( 905 nm ); scale bar, 250 μm . (d) High-resolution image of three beams in local plane; scale bar, 100 μm . (e) Typical PA signal pattern for three-beam detection scheme (triple peak marked with arrows); amplitude/time scale, 200 mV / div / 100 ms / div .

Fig. 3
Fig. 3

In vivo time-of-flight PAFC. (a) Typical PA signal trace and peak shapes for B16F10 cells, in mouse ear vessel ( 1064 nm laser). Peak-width distributions for (b) B16F10 cells in abdominal wall and ear blood vessels ( 1064 nm ), (c) different time frames after i.v. injection of GNR-820-CD-45 for targeting WBCs in mouse circulation ( 820 nm ), (d) i.v. injection of GNR-660-folate ( 671 nm ), and (e) i.v. injection of MDA-MB-231 breast cancer cells labeled in vitro by GNR-660-folate ( 671 nm ).

Fig. 4
Fig. 4

Scatter plot of height and width of peaks for label-free PAFC detection of circulating B16F10 cells in mouse ear arteriole ( 1064 nm ). Area I suggests signals from individual cells; area II includes aggregates of several cells; area III indicates possible rolling cells.

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