Abstract

Optical micro-angiography (OMAG) was developed to achieve volumetric imaging of the microstructures and dynamic cerebrovascular blood perfusion in mice with capillary level resolution and high signal-to-background ratio. In this paper, we present a high-speed and high-sensitivity OMAG imaging system by using an InGaAs line scan camera and broadband light source at 1.3 µm wavelength for enhanced imaging depth in tissue. We show that high quality imaging of cerebrovascular blood perfusion down to capillary level resolution with the intact skin and cranium are obtained in vivo with OMAG, without the interference from the blood perfusion in the overlaying skin. The results demonstrate the potential of 1.3µm OMAG for high-speed and high-sensitivity imaging of blood perfusion in human and small animal studies.

© 2007 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef]
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    [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
  28. C. Dorrer, N. Belabas, J. P. Likforman, and M. Joffre, "Spectral resolution and sampling issues in Fourier-transform spectral Interferometry," J. Opt. Soc. Am. B 17, 1795-1802 (2000).
    [CrossRef]
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2007 (3)

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. Hanson, and A. Gruber, "Three dimensional optical angiography," Opt. Express 15, 4083-4097 (2007).
[CrossRef] [PubMed]

L. Carrion, M. Lestrade, Z. Xu, G. Touma, R. Maciejko, and M. Bertrand, "Comparative study of optical sources in the near infrared for optical coherence tomography applications," J. Biomed. Opt. 12, 014017 (2007).
[CrossRef] [PubMed]

R. K. Wang, "In vivo full range complex Fourier Domain optical coherence tomography," Appl. Phys. Lett. 90, 054103 (2007).
[CrossRef]

2006 (5)

R. K. Wang and Z. H. Ma, "A practical approach to eliminate autocorrelation artefacts for volume-rate spectral domain optical coherence tomography," Phys. Med. Biol. 51, 3231-3239 (2006).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. H. V. Wang, "Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging," Nat. Biotechnol. 24, 848-851 (2006).
[CrossRef] [PubMed]

T. Misgeld and M. Kerschensteiner, "In vivo imaging of the diseased nervous system." Nat. Rev. Neurosci. 7, 449-463 (2006).
[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, 3001-3003 (2006).
[CrossRef] [PubMed]

R. K. Wang, Z. Ma, and S. J. Kirkpatrick, "Tissue Doppler optical coherence elastography for real time strain rate and strain mapping of soft tissue," Appl. Phys. Lett. 89, 144103 (2006).
[CrossRef]

2005 (1)

2003 (4)

S. H. Yun, G. J. Tearney, B. E. Bouma, B. H. Park, and J. F. de Boer, "High-speed spectral-domain optical coherence tomography at 1.3 μm wavelength," Opt. Express 11, 3598-3604 (2003).
[CrossRef] [PubMed]

X. D. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L.-H. Wang, "Non-invasive laser-induced photoacoustic tomography for structural and functional imaging of the brain in vivo," Nat. Biotechnol. 21, 803-806 (2003).
[CrossRef] [PubMed]

B. R. White, M. C. Pierce, N. Nassif,  et al., "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]

D. M. McDonald and P. L. Choyke, "Imaging of angiogenesis: from microscope to clinic," Nat. Med. 9, 713-725 (2003).
[CrossRef] [PubMed]

2002 (2)

T. P. Padera, B. R. Stoll, P. T. So, and R. K. Jain, "Conventional and high speed intravital multiphoton laser scanning microscopy of microvasculature, lymphatics, and leukocyte-endothelial interactions," Mol. Imaging 1, 9-15 (2002).
[CrossRef]

B. E. Bouma and G. J. Tearney, "Clinical imaging with optical coherence tomography," Acad. Radiol. 9, 942-953 (2002).
[CrossRef] [PubMed]

2001 (2)

R. K. Jain, "Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function," J. Controlled Release 74, 7-25 (2001).
[CrossRef]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, "Dynamic imaging of cerebral blood flow using Laser Speckle," J. Cereb. Blood Flow Metab. 21, 195-201 (2001).
[CrossRef] [PubMed]

2000 (3)

A. N. Nielsen, M. Fabricius, and M. Lauritzen. "Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression," J. Vasc. Res. 37, 513-522 (2000).
[CrossRef]

C. Dorrer, N. Belabas, J. P. Likforman, and M. Joffre, "Spectral resolution and sampling issues in Fourier-transform spectral Interferometry," J. Opt. Soc. Am. B 17, 1795-1802 (2000).
[CrossRef]

R. K. Wang, "Modelling optical properties of soft tissue by Fractal Distribution of Scatters," J. Mod. Opt. 47, 103-120 (2000)

1999 (1)

F. Calamante, D. L. Thomas, G. S. Pell, J. Wiersma, and R. Turner, "Measuring cerebral blood flow using magnetic resonance imaging techniques," J Cereb Blood Flow Metab 19, 701-735 (1999).
[CrossRef] [PubMed]

1998 (2)

Y. Pan, and D. L. Farkas, "Non-invasive imaging of living human skin with dual-wavelength optical coherence tomography in two and three dimensions," J. Biomed. Opt. 3, 446-465 (1998).
[CrossRef]

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

1997 (2)

Z. P. Chen, T. E. Milner, S. Srinivas,  et al., "Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography," Opt. Lett. 22, 1119-1121 (1997).
[CrossRef] [PubMed]

D. Malonek, U Dirnagl, U Lindauer, K Yamada, I Kanno, and A Grinvald, "Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation," Proc. Natl. Acad. Sci. USA 94,14826-14831 (1997).
[CrossRef]

1994 (2)

K. Hossmann, "Viability thresholds and the penumbra of focal ischemia," Ann Neurol 36, 557-565 (1994).
[CrossRef] [PubMed]

W. D. Heiss, R. Graf, K. Wienhard, J. Lottgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, "Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats," J Cereb Blood Flow Metab 14, 892-902 (1994).
[CrossRef] [PubMed]

1986 (1)

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324, 361-364 (1986).
[CrossRef] [PubMed]

1978 (1)

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, "Measurement of local cerebral blood flow with iodo [14C] antipyrine," Am J. Physiol. 234, H59-66 (1978).
[PubMed]

Acad. Radiol. (1)

B. E. Bouma and G. J. Tearney, "Clinical imaging with optical coherence tomography," Acad. Radiol. 9, 942-953 (2002).
[CrossRef] [PubMed]

Am J. Physiol. (1)

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, "Measurement of local cerebral blood flow with iodo [14C] antipyrine," Am J. Physiol. 234, H59-66 (1978).
[PubMed]

Ann Neurol (1)

K. Hossmann, "Viability thresholds and the penumbra of focal ischemia," Ann Neurol 36, 557-565 (1994).
[CrossRef] [PubMed]

Appl. Phys. Lett. (2)

R. K. Wang, Z. Ma, and S. J. Kirkpatrick, "Tissue Doppler optical coherence elastography for real time strain rate and strain mapping of soft tissue," Appl. Phys. Lett. 89, 144103 (2006).
[CrossRef]

R. K. Wang, "In vivo full range complex Fourier Domain optical coherence tomography," Appl. Phys. Lett. 90, 054103 (2007).
[CrossRef]

J Cereb Blood Flow Metab (2)

F. Calamante, D. L. Thomas, G. S. Pell, J. Wiersma, and R. Turner, "Measuring cerebral blood flow using magnetic resonance imaging techniques," J Cereb Blood Flow Metab 19, 701-735 (1999).
[CrossRef] [PubMed]

W. D. Heiss, R. Graf, K. Wienhard, J. Lottgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, "Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats," J Cereb Blood Flow Metab 14, 892-902 (1994).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

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

Y. Pan, and D. L. Farkas, "Non-invasive imaging of living human skin with dual-wavelength optical coherence tomography in two and three dimensions," J. Biomed. Opt. 3, 446-465 (1998).
[CrossRef]

L. Carrion, M. Lestrade, Z. Xu, G. Touma, R. Maciejko, and M. Bertrand, "Comparative study of optical sources in the near infrared for optical coherence tomography applications," J. Biomed. Opt. 12, 014017 (2007).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (1)

A. K. Dunn, H. Bolay, M. A. Moskowitz, and D. A. Boas, "Dynamic imaging of cerebral blood flow using Laser Speckle," J. Cereb. Blood Flow Metab. 21, 195-201 (2001).
[CrossRef] [PubMed]

J. Controlled Release (1)

R. K. Jain, "Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function," J. Controlled Release 74, 7-25 (2001).
[CrossRef]

J. Mod. Opt. (1)

R. K. Wang, "Modelling optical properties of soft tissue by Fractal Distribution of Scatters," J. Mod. Opt. 47, 103-120 (2000)

J. Opt. Soc. Am. B (1)

J. Vasc. Res. (1)

A. N. Nielsen, M. Fabricius, and M. Lauritzen. "Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression," J. Vasc. Res. 37, 513-522 (2000).
[CrossRef]

Mol. Imaging (1)

T. P. Padera, B. R. Stoll, P. T. So, and R. K. Jain, "Conventional and high speed intravital multiphoton laser scanning microscopy of microvasculature, lymphatics, and leukocyte-endothelial interactions," Mol. Imaging 1, 9-15 (2002).
[CrossRef]

Nat. Biotechnol. (2)

X. D. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L.-H. Wang, "Non-invasive laser-induced photoacoustic tomography for structural and functional imaging of the brain in vivo," Nat. Biotechnol. 21, 803-806 (2003).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. H. V. Wang, "Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging," Nat. Biotechnol. 24, 848-851 (2006).
[CrossRef] [PubMed]

Nat. Med. (1)

D. M. McDonald and P. L. Choyke, "Imaging of angiogenesis: from microscope to clinic," Nat. Med. 9, 713-725 (2003).
[CrossRef] [PubMed]

Nat. Rev. Neurosci. (1)

T. Misgeld and M. Kerschensteiner, "In vivo imaging of the diseased nervous system." Nat. Rev. Neurosci. 7, 449-463 (2006).
[CrossRef] [PubMed]

Nature (1)

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, "Functional architecture of cortex revealed by optical imaging of intrinsic signals," Nature 324, 361-364 (1986).
[CrossRef] [PubMed]

Opt. Express (4)

Opt. Lett. (2)

Phys. Med. Biol. (1)

R. K. Wang and Z. H. Ma, "A practical approach to eliminate autocorrelation artefacts for volume-rate spectral domain optical coherence tomography," Phys. Med. Biol. 51, 3231-3239 (2006).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA (1)

D. Malonek, U Dirnagl, U Lindauer, K Yamada, I Kanno, and A Grinvald, "Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation," Proc. Natl. Acad. Sci. USA 94,14826-14831 (1997).
[CrossRef]

Supplementary Material (2)

» Media 1: AVI (2394 KB)     
» Media 2: AVI (2584 KB)     

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Figures (6)

Fig. 1.
Fig. 1.

Schematic of the OMAG system operating at 1.3µm where SLD represents the superluminescent diode and PC the polarization controller.

Fig. 2.
Fig. 2.

Imaging of a solid scattering material to assess the noise level of OMAG imaging performance. 1000 and 2000 A scan spatial sampling density over 2.5 mm of B scan are given, respectively. (A) OCT/OMAG structural image, (B) OMAG flow image where there is almost no improvement when denser sampling approach is used, and (C) background noise level plotted as a function of depth in OMAG flow image, which results suggesting OMAG delivers superb flow imaging performance.

Fig. 3.
Fig. 3.

In vivo imaging of the finger nail bed of an adult volunteer (41 years age). Shown is a B scan consisting of 1000 A scans across 2.5mm. (A) Structural OCT/OMAG image where the nail plate and bed can be clearly visualized. (B) OMAG flow image where it is evident that the capillary blood flows within nail bed are abundant. The white bar indicates 500µm.

Fig. 4.
Fig. 4.

Cut away view of volume image rendered from 3-D micro-structural images of the mouse head obtained by OMAG system in vivo, where the important tissue layers, such as skin, skull bone and grey matter are clearly identified. The volume image given has a physical dimension of 2.5×2.5×2.0 mm3 in x-y-z direction as shown. See also the movie (2.5Mbytes); [Media 1]

Fig. 5.
Fig. 5.

Cerebral blood perfusion was imaged with OMAG in vivo with the intact skin and cranium. (A) volumetric rendering of fused 3D OMAG micro-structural and blood perfusion image. The volume size is 2.5×2.5×2.0 mm3, see also the associated movie for details (2.6Mbytes) [Media 2]; (B) projection image of blood flows from within the skin; (C) projection image of cerebro-vascular perfusion from brain cortex; and (D) Projection image from all depths.

Fig. 6.
Fig. 6.

The head of an adult mouse with the skin and skull intact was imaged with OMAG in vivo. (A) and (B) are the projection views of blood perfusion from within the skin and the brain cortex, respectively. Capillary blood flow can be seen from (B). It took ~7.5 minutes to acquire the 3-D data to obtain (A) and (B) using the current system setup. (C) Photograph taken right after the experiments where viewing the vasculatures through the skin is impossible. (D) Photograph showing blood vessels over the cortex after the skull and the skin of the same mouse were carefully removed. The superficial major blood vessels show excellent correspondence with those in (B). The area marked with dashed white box represents 4.2 by 7.2 mm2; and the scale bar indicates 1.0 mm.

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