Abstract

We describe a high-speed camera system for frequency domain imaging suitable for applications such as in vivo diffuse optical imaging and fluorescence lifetime imaging. 14-bit images are acquired at 2 gigapixels per second and analyzed with real-time pipeline processing using field programmable gate arrays (FPGAs). Performance of the camera system has been tested both for RF-modulated laser imaging in combination with a gain-modulated image intensifier and a simpler system based upon an LED light source. System amplitude and phase noise are measured and compared against theoretical expressions in the shot noise limit presented for different frequency domain configurations. We show the camera itself is capable of shot noise limited performance for amplitude and phase in as little as 3 ms, and when used in combination with the intensifier the noise levels are nearly shot noise limited. The best phase noise in a single pixel is 0.04 degrees for a 1 s integration time.

© 2011 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
    [CrossRef]
  2. E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
    [CrossRef] [PubMed]
  3. S. J. Madsen, E. R. Anderson, R. C. Haskell, and B. J. Tromberg, “Portable, high-bandwidth frequency-domain photon migration instrument for tissue spectroscopy,” Opt. Lett. 19(23), 1934–1936 (1994).
    [CrossRef] [PubMed]
  4. H. Jiang, K. D. Paulsen, U. L. Osterberg, B. W. Pogue, and M. S. Patterson, “Simultaneous reconstruction of optical absorption and scattering maps in turbid media from near-infrared frequency-domain data,” Opt. Lett. 20(20), 2128–2130 (1995).
    [CrossRef] [PubMed]
  5. M. Gerken and G. W. Faris, “High-precision frequency-domain measurements of the optical properties of turbid media,” Opt. Lett. 24(14), 930–932 (1999).
    [CrossRef] [PubMed]
  6. V. Toronov, E. D’Amico, D. Hueber, E. Gratton, B. Barbieri, and A. Webb, “Optimization of the signal-to-noise ratio of frequency-domain instrumentation for near-infrared spectro-imaging of the human brain,” Opt. Express 11(21), 2717–2729 (2003).
    [CrossRef] [PubMed]
  7. A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt. 8(1), 111–120 (2003).
    [CrossRef] [PubMed]
  8. S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008).
    [CrossRef] [PubMed]
  9. T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
    [CrossRef]
  10. J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
    [CrossRef]
  11. R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
    [CrossRef] [PubMed]
  12. K. Zhang and J. U. Kang, “Real-time intraoperative 4D full-range FD-OCT based on the dual graphics processing units architecture for microsurgery guidance,” Biomed. Opt. Express 2(4), 764–770 (2011).
    [CrossRef] [PubMed]
  13. A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
    [CrossRef] [PubMed]
  14. J. R. Janesick, “Scientific Charge-Coupled Devices,” (SPIE Press, Bellingham, Washington, 2001), pp. 101–105.
  15. D. F. Walls, “Squeezed states of light,” Nature 306(5939), 141–146 (1983).
    [CrossRef]
  16. X. Gu, K. Ren, and A. H. Hielscher, “Frequency-domain sensitivity analysis for small imaging domains using the equation of radiative transfer,” Appl. Opt. 46(10), 1624–1632 (2007).
    [CrossRef] [PubMed]
  17. T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
    [CrossRef] [PubMed]

2011 (1)

2009 (1)

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

2008 (2)

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
[CrossRef] [PubMed]

S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008).
[CrossRef] [PubMed]

2007 (1)

2003 (2)

V. Toronov, E. D’Amico, D. Hueber, E. Gratton, B. Barbieri, and A. Webb, “Optimization of the signal-to-noise ratio of frequency-domain instrumentation for near-infrared spectro-imaging of the human brain,” Opt. Express 11(21), 2717–2729 (2003).
[CrossRef] [PubMed]

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt. 8(1), 111–120 (2003).
[CrossRef] [PubMed]

2002 (1)

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

1999 (1)

1998 (1)

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

1995 (1)

1994 (1)

1992 (1)

T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
[CrossRef]

1991 (2)

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[CrossRef]

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

1983 (1)

D. F. Walls, “Squeezed states of light,” Nature 306(5939), 141–146 (1983).
[CrossRef]

Anderson, E. R.

Barbieri, B.

Berndt, K. W.

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[CrossRef]

Bouma, B. E.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Chance, B.

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Chen, Y.

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

Colyer, R. A.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
[CrossRef] [PubMed]

Cope, M.

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

Culver, J. P.

S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008).
[CrossRef] [PubMed]

D’Amico, E.

Desjardins, A. E.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Faris, G. W.

French, T.

T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
[CrossRef]

Gerken, M.

Gratton, E.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
[CrossRef] [PubMed]

V. Toronov, E. D’Amico, D. Hueber, E. Gratton, B. Barbieri, and A. Webb, “Optimization of the signal-to-noise ratio of frequency-domain instrumentation for near-infrared spectro-imaging of the human brain,” Opt. Express 11(21), 2717–2729 (2003).
[CrossRef] [PubMed]

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
[CrossRef]

Gu, X.

Haskell, R. C.

Hielscher, A. H.

Hueber, D.

Intes, X.

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

Jiang, H.

Kang, J. U.

Lakowicz, J. R.

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[CrossRef]

Lee, C.

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
[CrossRef] [PubMed]

Leigh, J.

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Madsen, S. J.

Maier, J.

T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
[CrossRef]

Maris, M.

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Nioka, S.

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Osterberg, U. L.

Patterson, M. S.

Patwardhan, S. V.

S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008).
[CrossRef] [PubMed]

Paulsen, K. D.

Pogue, B. W.

Ramanujam, N.

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

Ren, K.

Sevick, E. M.

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt. 8(1), 111–120 (2003).
[CrossRef] [PubMed]

Suter, M. J.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Tearney, G. J.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Thompson, A. B.

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt. 8(1), 111–120 (2003).
[CrossRef] [PubMed]

Toronov, V.

Tromberg, B.

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

Tromberg, B. J.

Tu, T.

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

Vakoc, B. J.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Walls, D. F.

D. F. Walls, “Squeezed states of light,” Nature 306(5939), 141–146 (1983).
[CrossRef]

Webb, A.

Yun, S. H.

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

Zhang, J.

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

Zhang, K.

Anal. Biochem. (1)

E. M. Sevick, B. Chance, J. Leigh, S. Nioka, and M. Maris, “Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation,” Anal. Biochem. 195(2), 330–351 (1991).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

IEEE Trans. Med. Imaging (1)

A. E. Desjardins, B. J. Vakoc, M. J. Suter, S. H. Yun, G. J. Tearney, and B. E. Bouma, “Real-time FPGA processing for high-speed optical frequency domain imaging,” IEEE Trans. Med. Imaging 28(9), 1468–1472 (2009).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

A. B. Thompson and E. M. Sevick-Muraca, “Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy,” J. Biomed. Opt. 8(1), 111–120 (2003).
[CrossRef] [PubMed]

S. V. Patwardhan and J. P. Culver, “Quantitative diffuse optical tomography for small animals using an ultrafast gated image intensifier,” J. Biomed. Opt. 13(1), 011009 (2008).
[CrossRef] [PubMed]

T. Tu, Y. Chen, J. Zhang, X. Intes, and B. Chance, “Analysis on performance and optimization of frequency-domain near-infrared instruments,” J. Biomed. Opt. 7(4), 643–649 (2002).
[CrossRef] [PubMed]

Microsc. Res. Tech. (1)

R. A. Colyer, C. Lee, and E. Gratton, “A novel fluorescence lifetime imaging system that optimizes photon efficiency,” Microsc. Res. Tech. 71(3), 201–213 (2008).
[CrossRef] [PubMed]

Nature (1)

D. F. Walls, “Squeezed states of light,” Nature 306(5939), 141–146 (1983).
[CrossRef]

Opt. Express (1)

Opt. Lett. (3)

Proc. SPIE (1)

T. French, J. Maier, and E. Gratton, “Frequency domain imaging of thick tissues using a CCD,” Proc. SPIE 1640, 254–261 (1992).
[CrossRef]

Rev. Sci. Instrum. (2)

J. R. Lakowicz and K. W. Berndt, “Lifetime-selective fluorescence imaging using an rf phase-sensitive camera,” Rev. Sci. Instrum. 62(7), 1727–1734 (1991).
[CrossRef]

B. Chance, M. Cope, E. Gratton, N. Ramanujam, and B. Tromberg, “Phase measurement of light absorption and scatter in human tissue,” Rev. Sci. Instrum. 69(10), 3457–3481 (1998).
[CrossRef]

Other (1)

J. R. Janesick, “Scientific Charge-Coupled Devices,” (SPIE Press, Bellingham, Washington, 2001), pp. 101–105.

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 (8)

Fig. 1
Fig. 1

Schematic of optical and electrical circuits.

Fig. 2
Fig. 2

Schematic of signal flow on FPGA boards.

Fig. 3
Fig. 3

Schematic of RF circuitry.

Fig. 4
Fig. 4

Examples of DC image, AC image, and phase image using LED illumination. The graphs under each image show the pixel counts at row 300. The units of the DC and AC images are the summation of the pixel counts from each image. Using a range of intensities in a single image is useful for studying the limiting noise behavior as described below.

Fig. 5
Fig. 5

Measured vs theoretical noise from the LED system from images with 1000 frames and 20 LED cycles. The x axes for Figs. 5-7 are total counts summed over all frames (1000 frames for this figure). Note that the AC CV (coefficient of variation) and phase standard deviation are almost identical. The best measured phase noise is 0.0007 radians or 0.04 degrees.

Fig. 6
Fig. 6

Measured vs theoretical noise from the LED system from images with 3 and 10 frames and 1 LED cycle. Note that the AC CV and phase standard deviation deviate for large amplitude with 3 frames per cycles—this effect is elucidated in Fig. 8.

Fig. 7
Fig. 7

Measured vs actual noise from image intensifier system with 400 frames and 20 cycles. AC/DC ratios vs DC amplitude. Different colors indicate different phase shifts.

Fig. 8
Fig. 8

Measured and theoretical AC noise ratios per phase taken with phase increments of 10 degrees.

Tables (9)

Tables Icon

Table 1 Parameters for System Tests using LED and Laser

Tables Icon

Table 2 Linearity measurements for LED image data taken over 1s with LED phase changes (α) and FPGA phase changes (γ)

Tables Icon

Table 3 Linearity measurements for image intensifier data taken over 1s

Tables Icon

Table 4 Linearity measurements for LED image data taken at ≤ 10ms

Tables Icon

Table 7 Signal and variance for different types of frequency domain measurements

Tables Icon

Table 9 Expressions for Cases 1A and 2A with three evenly spaced measurements per modulation cycle (np = 3).

Tables Icon

Table 5 Cases considered for frequency domain measurements

Tables Icon

Table 6 Electrical modulation and analysis demodulation terms for different frequency domain measurement types

Tables Icon

Table 8 Dimensionless noise expressions for different types of frequency domain measurements

Equations (11)

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

X = n = 0 K 1 S ( n Δ t ) cos ( ω n Δ t + γ ) Δ t  and  Y = n = 0 K 1 S ( n Δ t ) sin ( ω n Δ t + γ ) Δ t
A = ( X 2 + Y 2 ) 1 / 2 ,
ϕ = t a n 1 ( X / Y ) .
σ A 2 A 2 = cos 2 ( ϕ ) σ X 2 + sin 2 ( ϕ ) σ Y 2 + sin ( 2 ϕ ) σ X Y 2 A 2 ,
σ ϕ 2 = sin 2 ( ϕ ) σ X 2 + cos 2 ( ϕ ) σ Y 2 sin ( 2 ϕ ) σ X Y 2 A 2 ,
N Δ t ( t ) = i d c Δ t q [ 1 + m 1 cos ( ω 1 t + α ) ]
σ N Δ t ( t ) = N Δ t ( t ) = i d c Δ t q [ 1 + m 1 cos ( ω 1 t + α ) ] .
S Δ t ( t ) = N Δ t ( t ) E ( t ) ,
σ S ( t ) = N Δ t ( t ) E ( t ) ,
X = T / 2 T / 2 S ( t ) cos ( ω t + γ ) d t = T / 2 T / 2 N Δ t ( t ) E ( t ) C ( t ) d t .
σ x 2 = T / 2 T / 2 σ N Δ t 2 ( t ) [ E ( t ) ] 2 [ C ( t ) ] 2 d t = T / 2 T / 2 N Δ t ( t ) [ E ( t ) ] 2 [ C ( t ) ] 2 d t .

Metrics