Abstract

We propose a Doppler optical micro-angiography (DOMAG) method to image flow velocities of the blood flowing in functional vessels within microcirculatory tissue beds in vivo. The method takes the advantages of recently developed optical micro-angiography (OMAG) technology, in which the endogenous optical signals backscattered from the moving blood cells are isolated from those originated from the tissue background, i.e., the tissue microstructures. The phase difference between adjacent A scans of OMAG flow signals is used to evaluate the flow velocity, similar to phase-resolved Doppler optical coherence tomography (PRDOCT). To meet the requirement of correlation between adjacent A scans in using the phase resolved technique to evaluate flow velocity, an ideal tissue-sample background (i.e., optically homogeneous tissue sample) is digitally reconstructed to replace the signals that represent the heterogeneous features of the static sample that are rejected in the OMAG flow images. Because of the ideal optical-homogeneous sample, DOMAG is free from the characteristic texture pattern noise due to the heterogeneous property of sample, leading to dramatic improvement of the imaging performance. A series of phantom flow experiments are performed to evaluate quantitatively the improved imaging performance. We then conduct in vivo experiments on a mouse brain to demonstrate that DOMAG is capable of quantifying the flow velocities within cerebrovascular network, down to capillary level resolution. Finally, we compare the in vivo imaging performance of DOMAG with that of PRDOCT, and show that DOMAG delivers at least 15-fold increase over the PRDOCT method in terms of the lower limit of flow velocity that can be detected.

© 2009 OSA

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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef]
  21. R. K. Wang, “Fourier domain optical coherence tomography achieves full range complex imaging in vivo by introducing a carrier frequency during scanning,” Phys. Med. Biol. 52(19), 5897–5907 (2007).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  23. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three Dimensional Optical Angiography,” Opt. Express 15(7), 4083–4097 (2007).
    [CrossRef] [PubMed]
  24. R. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 ?m wavelength,” Opt. Express 15(18), 11402–11412 (2007).
    [CrossRef] [PubMed]
  25. R. K. Wang, “Three dimensional optical angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo,” Phys. Med. Biol. 52(531–N), 537 (2007).
    [CrossRef]
  26. L. An and R. K. Wang, “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express 16(15), 11438–11452 (2008).
    [CrossRef] [PubMed]
  27. M. Mujat, R. C. Chan, B. Cense, B. H. Park, C. Joo, T. Akkin, T. C. Chen, and J. F. de Boer, “Retinal nerve fiber layer thickness map determined from optical coherence tomography images,” Opt. Express 13(23), 9480–9491 (2005).
    [CrossRef] [PubMed]
  28. V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis. ISBN number: 0819464333. SPIE (2007)
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    [CrossRef] [PubMed]

2008 (2)

2007 (7)

2006 (4)

2005 (4)

2004 (2)

2003 (5)

2002 (1)

1998 (1)

G. Häusler and M. W. Lindner, “Coherence radar and Spectral radar- new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998).
[CrossRef]

1997 (1)

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Akkin, T.

An, L.

Bachmann, A. H.

Bajraszewski, T.

Berisha, F.

Blatter, C.

Bouma, B. E.

Cense, B.

Chan, R. C.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, T. C.

Chen, Z. P.

Choma, M. A.

Cobb, M. J.

de Boer, J. F.

Ding, Z. H.

Drexler, W.

Fercher, A. F.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gruber, A.

Hanson, S. R.

Häusler, G.

G. Häusler and M. W. Lindner, “Coherence radar and Spectral radar- new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998).
[CrossRef]

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hitzenberger, C. K.

Hong, Y.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hurst, S.

Izatt, J. A.

Jacques, S. L.

Joo, C.

Kowalczyk, A.

Lasser, T.

A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Resonant Doppler flow imaging and optical vivisection of retinal blood vessels,” Opt. Express 15, 408–422 (2007).
[CrossRef] [PubMed]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography – principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[CrossRef]

Leitgeb, R.

Leitgeb, R. A.

Li, X.

Li, X. D.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Lindner, M. W.

G. Häusler and M. W. Lindner, “Coherence radar and Spectral radar- new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998).
[CrossRef]

Ma, Z.

Ma, Z. H.

MacDonald, D. J.

Makita, S.

Malekafzali, A.

Milner, T. E.

Mujat, M.

Nassif, N.

Nelson, J. S.

Park, B. H.

Pierce, M. C.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Ren, H.

Ren, H. W.

Sarunic, M. V.

Schmetterer, L.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Srinivas, S.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sun, T.

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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Szkulmowska, A.

Szkulmowski, M.

Tearney, G. J.

Tomlins, P. H.

P. H. Tomlins and R. K. Wang, “Theory, development and applications of optical coherence tomography,” J. Phys. D Appl. Phys. 38(15), 2519–2535 (2005).
[CrossRef]

Vakoc, B. J.

van Gemert, M. J. C.

Villiger, M. L.

Wang, R. K.

L. An and R. K. Wang, “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express 16(15), 11438–11452 (2008).
[CrossRef] [PubMed]

R. K. Wang, “Three dimensional optical angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo,” Phys. Med. Biol. 52(531–N), 537 (2007).
[CrossRef]

R. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 ?m wavelength,” Opt. Express 15(18), 11402–11412 (2007).
[CrossRef] [PubMed]

L. An and R. K. Wang, “Use of a scanner to modulate spatial interferograms for in vivo full-range Fourier-domain optical coherence tomography,” Opt. Lett. 32(23), 3423–3425 (2007).
[CrossRef] [PubMed]

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three Dimensional Optical Angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

R. K. Wang, “In vivo full rang complex Fourier domain optical coherence tomography,” Appl. Phys. Lett. 90(5), 054103 (2007).
[CrossRef]

R. K. Wang, “Fourier domain optical coherence tomography achieves full range complex imaging in vivo by introducing a carrier frequency during scanning,” Phys. Med. Biol. 52(19), 5897–5907 (2007).
[CrossRef] [PubMed]

R. K. Wang and Z. H. Ma, “Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography,” Opt. Lett. 31(20), 3001–3003 (2006).
[CrossRef] [PubMed]

P. H. Tomlins and R. K. Wang, “Theory, development and applications of optical coherence tomography,” J. Phys. D Appl. Phys. 38(15), 2519–2535 (2005).
[CrossRef]

Wang, X.

White, B. R.

Wojtkowski, M.

Yamanari, M.

Yang, C. H.

Yasuno, Y.

Yatagai, T.

Yun, S. H.

Zawadzki, R. J.

Zhang, J.

Zhao, Y. H.

Appl. Phys. Lett. (1)

R. K. Wang, “In vivo full rang complex Fourier domain optical coherence tomography,” Appl. Phys. Lett. 90(5), 054103 (2007).
[CrossRef]

J. Biomed. Opt. (1)

G. Häusler and M. W. Lindner, “Coherence radar and Spectral radar- new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998).
[CrossRef]

J. Phys. D Appl. Phys. (1)

P. H. Tomlins and R. K. Wang, “Theory, development and applications of optical coherence tomography,” J. Phys. D Appl. Phys. 38(15), 2519–2535 (2005).
[CrossRef]

Opt. Express (15)

S. H. Yun, G. J. Tearney, J. F. de Boer, and B. E. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
[CrossRef] [PubMed]

J. Zhang and Z. P. Chen, “In vivo blood flow imaging by a swept laser source based Fourier domain optical Doppler tomography,” Opt. Express 13(19), 7449–7459 (2005).
[CrossRef] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express 13(14), 5483–5492 (2005).
[CrossRef] [PubMed]

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11, 3116–3121 (2003).
[CrossRef] [PubMed]

B. R. White, M. C. Pierce, and N. Nassif, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical Doppler tomography,” Opt. Express 11, 3490–3497 (2003).
[CrossRef] [PubMed]

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
[CrossRef] [PubMed]

R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, “Performance of Fourier domain vs. time domain optical coherence tomography,” Opt. Express 11, 889–894 (2003).
[CrossRef] [PubMed]

M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11(18), 2183–2189 (2003).
[CrossRef] [PubMed]

A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Resonant Doppler flow imaging and optical vivisection of retinal blood vessels,” Opt. Express 15, 408–422 (2007).
[CrossRef] [PubMed]

M. Szkulmowski, A. Szkulmowska, T. Bajraszewski, A. Kowalczyk, and M. Wojtkowski, “Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 16(9), 6008–6025 (2008).
[CrossRef] [PubMed]

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three Dimensional Optical Angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

R. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 ?m wavelength,” Opt. Express 15(18), 11402–11412 (2007).
[CrossRef] [PubMed]

L. An and R. K. Wang, “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express 16(15), 11438–11452 (2008).
[CrossRef] [PubMed]

M. Mujat, R. C. Chan, B. Cense, B. H. Park, C. Joo, T. Akkin, T. C. Chen, and J. F. de Boer, “Retinal nerve fiber layer thickness map determined from optical coherence tomography images,” Opt. Express 13(23), 9480–9491 (2005).
[CrossRef] [PubMed]

H. Ren and X. Li, “Clutter rejection filters for optical Doppler tomography,” Opt. Express 14(13), 6103–6112 (2006).
[CrossRef] [PubMed]

Opt. Lett. (6)

Phys. Med. Biol. (2)

R. K. Wang, “Three dimensional optical angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo,” Phys. Med. Biol. 52(531–N), 537 (2007).
[CrossRef]

R. K. Wang, “Fourier domain optical coherence tomography achieves full range complex imaging in vivo by introducing a carrier frequency during scanning,” Phys. Med. Biol. 52(19), 5897–5907 (2007).
[CrossRef] [PubMed]

Rep. Prog. Phys. (1)

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography – principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[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, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Other (1)

V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis. ISBN number: 0819464333. SPIE (2007)

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Figures (10)

Fig. 1
Fig. 1

Schematic of the OMAG system used in this study to image the velocities of blood flow, where PC represents the polarization controller and CCD the charged coupled device. The laser diode emitting the light at 633 nm was used for aiming purposes during imaging.

Fig. 2
Fig. 2

Diagram of frequency components for different tissue sample: (A) an ideal tissue sample (optically homogeneous sample) with no moving particles; (B) a real tissue sample (optically heterogeneous sample) with no moving particles; (C) a real tissue sample (optically heterogeneous sample) with moving particles.

Fig. 3
Fig. 3

, Flow chart showing the steps for DOMAG to evaluate the velocities of blood flow from a B scan data set, I(k,t). The data coordinates are indicated in the lower right corner of each data block, where t is the time variable of probe beam scanning over a sample, k is the wavenumber, f is the spatial frequency, and z is the imaging depth. FT| t represents the Fourier transform (FT) against the time variable t in the B scan, FT−1 | f indicates the inverse FT against the spatial frequency, f, and FT|k is FT against the wavenumber k.

Fig. 4
Fig. 4

Flow Phantom experiment results. (A), OMAG structural image; (B) OMAG flow image; (C), DOMAG velocity image; (D) PRDOCT velocity image; and (E) flow signal profiles extracted from the positions marked in (C) and (D). See text for the marked regions in (A)

Fig. 5
Fig. 5

In vivo OMAG imaging results for a typical B scan of a mouse brain with the skull left intact. (A) OMAG image of microstructures, identical to conventional SDOCT image; (B) the corresponding OMAG image of blood flow; and (C) the corresponding DOMAG image of velocities of the blood flow.

Fig. 6
Fig. 6

In vivo 3D OMAG imaging of the cortical brain of a mouse with the skull left intact. The volumetric visualization was rendered by (A) merging the 3D micro-structural image with the 3D cerebral blood flow image, (B) the 3D signals of cerebral blood flow only, and (C) the corresponding DOMAG imaging of velocities within the 3D blood flow network in (B). The red color in (C) represents the blood moves towards the incident probe beam, and otherwise the green color. The physical image size was 2.5x2.5x2.0 (x-y-z) mm3.

Fig. 7
Fig. 7

Maximum projection view (x-y) of (A) OMAG and (B) DOMAG of the cerebral blood flow in the cortical brain of the mouse shown in Fig. 6.

Fig. 8
Fig. 8

Comparison between OMAG and PRDOCT B scan imaging of the cortical brain in mice in vivo. (A) OMAG structural image (i.e. SDOCT) and the corresponding (B) OMAG flow image, (C) DOMAG flow velocity image, and (D) PRDOCT flow velocity image, respectively. See the text for explanation of the arrows.

Fig. 9
Fig. 9

Comparison between 3D OMAG and PRDOCT imaging of the cortical brain in mice with the intact skull in vivo. Shown are the maximum x-y projection views of (A) OMAG cerebral blood flow image, (B) DOMAG flow velocity image and (C) PRDOCT flow velocity image, respectively. The physical size of scanned tissue volume was 2.5x2.5x2.0 mm3. White bar = 500 μm.

Fig. 10
Fig. 10

3D plot of a typical B scan of flow images. (A) Conventional PRDOCT flow image without segmentation; (B) conventional PRDOCT flow image with segmentation; and (C) Doppler OMAG flow image.

Tables (1)

Tables Icon

Table 1 Evaluated phase noise, effective signal and phase SNR of phase differences for DOMAG and PRDOCT

Equations (14)

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

I(k)j=S(kj)|ERexp(i2kjr)+a(z)exp{i2kj[r+nz]}dz|2j=1,2,3...1024
I(k,jt)=S(kj)|ERexp(i2kjr)+a(z,t)exp{i2kj[r+nz]}dz|2
I(kj,t)=2S(kj)ERa(z,t)cos(2kjnz)dz
I(kj,t)=2S(kj)ERa(z,t)cos(2kjn(z,t)z)dz
I(kj,t)=2S(kj)ER[a(z,t)cos(2kjn(z,t)z)dz+a(z1,t1)cos[2kjn(z1,t1)(z1vt)]]
I0(kj,t)=2S(kj)ERa0(z,t)cos(2kjn0(z,t)z)dz
I(kj,t)=2S(kj){ERa0cos(2kjn0z)dz+ERa(z1,t1)cos[2kjn(z1,t1)(z1vt)]}
I˜(z,t)=FT1{I(kj,t)}|k=A(z,t)exp[iφ(z,t)]
Δφ(z,t)=tan1[Im[I˜(z,tn)I˜(z,tn1)]Re[I˜(z,tn)I˜(z,tn1)]].
v(z,t)=λΔφ(z,t)4πΔt
σΔφ=1M1ΩN(ΔφΔφ¯)2
S=ΩS(Δφ>σΔφ)×Δφ
Phase    SNR=20×log(S/σΔφ)
σΔφ2=(1X)

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