Abstract

Chronically monitoring cerebral activities in awake and freely moving status is very important in physiological and pathological studies. We present a novel standalone micro-imager for monitoring the cerebral blood flow (CBF) and total hemoglobin (HbT) activities in freely moving animals using the laser speckle contrast imaging (LSCI) and optical intrinsic signal (OIS) methods. A new cranial window method, using contact lens and wide field optics, is also proposed to achieve the chronic and wide-field imaging of rat’s cerebral cortex. The hemodynamic activities of rats’ cortex were measured for the first time without restriction of cables or fibers in awake and behaving animals. Chronic imaging showed the increase of CBF and HbT in motor cortex when the rats were climbing on the cage wall. Interestingly, the CBF activation of supplying vessel was smaller than that of parenchyma. Furthermore, after the climbing, CBF demonstrated fully return to the baseline while HbT showed a delayed recovery. The standalone micro-imager technology provides new possibilities of brain imaging in cognitive neuroscience studies.

© 2016 Optical Society of America

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2016 (1)

2013 (2)

2012 (4)

A. Rege, J. Senarathna, N. Li, and N. V. Thakor, “Anisotropic processing of laser speckle images improves spatiotemporal resolution,” IEEE Trans. Biomed. Eng. 59(5), 1272–1280 (2012).
[Crossref] [PubMed]

O. Yang and B. Choi, “Laser speckle imaging using a consumer-grade color camera,” Opt. Lett. 37(19), 3957–3959 (2012).
[Crossref] [PubMed]

K. M. Tye and K. Deisseroth, “Optogenetic investigation of neural circuits underlying brain disease in animal models,” Nat. Rev. Neurosci. 13(4), 251–266 (2012).
[Crossref] [PubMed]

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab. 32(7), 1277–1309 (2012).
[Crossref] [PubMed]

2011 (5)

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt. 16(9), 090502 (2011).
[Crossref] [PubMed]

J. W. Lichtman and W. Denk, “The big and the small: challenges of imaging the brain’s circuits,” Science 334(6056), 618–623 (2011).
[Crossref] [PubMed]

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

A. Rege, K. Murari, A. Seifert, A. P. Pathak, and N. V. Thakor, “Multiexposure laser speckle contrast imaging of the angiogenic microenvironment,” J. Biomed. Opt. 16(5), 056006 (2011).
[Crossref] [PubMed]

2010 (4)

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15(1), 011109 (2010).
[Crossref] [PubMed]

P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
[Crossref] [PubMed]

C. M. Niell and M. P. Stryker, “Modulation of visual responses by behavioral state in mouse visual cortex,” Neuron 65(4), 472–479 (2010).
[Crossref] [PubMed]

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

2009 (2)

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. D. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

2008 (3)

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[Crossref] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
[Crossref] [PubMed]

A. B. Parthasarathy, W. J. Tom, A. Gopal, X. Zhang, and A. K. Dunn, “Robust flow measurement with multi-exposure speckle imaging,” Opt. Express 16(3), 1975–1989 (2008).
[Crossref] [PubMed]

2007 (1)

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

2006 (1)

A. K. Lee, I. D. Manns, B. Sakmann, and M. Brecht, “Whole-cell recordings in freely moving rats,” Neuron 51(4), 399–407 (2006).
[Crossref] [PubMed]

2003 (1)

2002 (1)

N. Pouratian, A. F. Cannestra, N. A. Martin, and A. W. Toga, “Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping,” Neurosurg. Focus 13(4), e1 (2002).
[Crossref] [PubMed]

2001 (2)

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(3), 195–201 (2001).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

2000 (1)

E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[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(6095), 361–364 (1986).
[Crossref] [PubMed]

Adelman, T. L.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Agrochão, M.

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

Akassoglou, K.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

Andermann, M. L.

Arieli, A.

E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[PubMed]

Barretto, R. P. J.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
[Crossref] [PubMed]

Blinder, P.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

Boas, D. A.

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15(1), 011109 (2010).
[Crossref] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett. 28(1), 28–30 (2003).
[Crossref] [PubMed]

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(3), 195–201 (2001).
[Crossref] [PubMed]

Bolay, H.

Bonhoeffer, T.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Brecht, M.

A. K. Lee, I. D. Manns, B. Sakmann, and M. Brecht, “Whole-cell recordings in freely moving rats,” Neuron 51(4), 399–407 (2006).
[Crossref] [PubMed]

Burns, L. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
[Crossref] [PubMed]

Cannestra, A. F.

N. Pouratian, A. F. Cannestra, N. A. Martin, and A. W. Toga, “Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping,” Neurosurg. Focus 13(4), e1 (2002).
[Crossref] [PubMed]

Carlen, P. L.

Choi, B.

Chow, D. K.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Chuckowree, J.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Cocker, E. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
[Crossref] [PubMed]

Collman, F.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Dabrowski, W.

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

Dale, A. M.

Davalos, D.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

De Paola, V.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Deisseroth, K.

K. M. Tye and K. Deisseroth, “Optogenetic investigation of neural circuits underlying brain disease in animal models,” Nat. Rev. Neurosci. 13(4), 251–266 (2012).
[Crossref] [PubMed]

Denk, W.

J. W. Lichtman and W. Denk, “The big and the small: challenges of imaging the brain’s circuits,” Science 334(6056), 618–623 (2011).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. D. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Devor, A.

Dombeck, D. A.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Drew, P. J.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab. 32(7), 1277–1309 (2012).
[Crossref] [PubMed]

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Li, B.

Li, N.

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Li, P.

Li, Y.

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T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
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T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
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P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
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Mostany, R.

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[Crossref] [PubMed]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
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N. Pouratian, A. F. Cannestra, N. A. Martin, and A. W. Toga, “Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping,” Neurosurg. Focus 13(4), e1 (2002).
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A. Rege, J. Senarathna, N. Li, and N. V. Thakor, “Anisotropic processing of laser speckle images improves spatiotemporal resolution,” IEEE Trans. Biomed. Eng. 59(5), 1272–1280 (2012).
[Crossref] [PubMed]

A. Rege, K. Murari, A. Seifert, A. P. Pathak, and N. V. Thakor, “Multiexposure laser speckle contrast imaging of the angiogenic microenvironment,” J. Biomed. Opt. 16(5), 056006 (2011).
[Crossref] [PubMed]

P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
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Sakmann, B.

A. K. Lee, I. D. Manns, B. Sakmann, and M. Brecht, “Whole-cell recordings in freely moving rats,” Neuron 51(4), 399–407 (2006).
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J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. D. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
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A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab. 32(7), 1277–1309 (2012).
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K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
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B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
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A. Rege, K. Murari, A. Seifert, A. P. Pathak, and N. V. Thakor, “Multiexposure laser speckle contrast imaging of the angiogenic microenvironment,” J. Biomed. Opt. 16(5), 056006 (2011).
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A. Rege, J. Senarathna, N. Li, and N. V. Thakor, “Anisotropic processing of laser speckle images improves spatiotemporal resolution,” IEEE Trans. Biomed. Eng. 59(5), 1272–1280 (2012).
[Crossref] [PubMed]

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T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
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A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab. 32(7), 1277–1309 (2012).
[Crossref] [PubMed]

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

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E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[PubMed]

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T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
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Sigal, I.

Slovin, H.

E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[PubMed]

Stefanovic, B.

Stryker, M. P.

C. M. Niell and M. P. Stryker, “Modulation of visual responses by behavioral state in mouse visual cortex,” Neuron 65(4), 472–479 (2010).
[Crossref] [PubMed]

Svoboda, K.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Szuts, T. A.

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

Tank, D. W.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Thakor, N. V.

A. Rege, J. Senarathna, N. Li, and N. V. Thakor, “Anisotropic processing of laser speckle images improves spatiotemporal resolution,” IEEE Trans. Biomed. Eng. 59(5), 1272–1280 (2012).
[Crossref] [PubMed]

A. Rege, K. Murari, A. Seifert, A. P. Pathak, and N. V. Thakor, “Multiexposure laser speckle contrast imaging of the angiogenic microenvironment,” J. Biomed. Opt. 16(5), 056006 (2011).
[Crossref] [PubMed]

P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
[Crossref] [PubMed]

Toga, A. W.

N. Pouratian, A. F. Cannestra, N. A. Martin, and A. W. Toga, “Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping,” Neurosurg. Focus 13(4), e1 (2002).
[Crossref] [PubMed]

Tom, W. J.

Tong, S.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt. 16(9), 090502 (2011).
[Crossref] [PubMed]

P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
[Crossref] [PubMed]

Trachtenberg, J. T.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Tsai, P. S.

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

Tye, K. M.

K. M. Tye and K. Deisseroth, “Optogenetic investigation of neural circuits underlying brain disease in animal models,” Nat. Rev. Neurosci. 13(4), 251–266 (2012).
[Crossref] [PubMed]

Uchida, N.

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

Vanzetta, I.

E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[PubMed]

Wallace, D. J.

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. D. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Wang, J.

Wang, Y.

Wiesel, T. N.

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(6095), 361–364 (1986).
[Crossref] [PubMed]

Wilbrecht, L.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Yang, O.

Yin, C.

Zhang, X.

Ziv, Y.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

IEEE Trans. Biomed. Eng. (2)

P. Miao, A. Rege, N. Li, N. V. Thakor, and S. Tong, “High resolution cerebral blood flow imaging by registered laser speckle contrast analysis,” IEEE Trans. Biomed. Eng. 57(5), 1152–1157 (2010).
[Crossref] [PubMed]

A. Rege, J. Senarathna, N. Li, and N. V. Thakor, “Anisotropic processing of laser speckle images improves spatiotemporal resolution,” IEEE Trans. Biomed. Eng. 59(5), 1272–1280 (2012).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

A. Rege, K. Murari, A. Seifert, A. P. Pathak, and N. V. Thakor, “Multiexposure laser speckle contrast imaging of the angiogenic microenvironment,” J. Biomed. Opt. 16(5), 056006 (2011).
[Crossref] [PubMed]

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15(1), 011109 (2010).
[Crossref] [PubMed]

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt. 16(9), 090502 (2011).
[Crossref] [PubMed]

J. Cereb. Blood Flow Metab. (2)

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab. 32(7), 1277–1309 (2012).
[Crossref] [PubMed]

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(3), 195–201 (2001).
[Crossref] [PubMed]

J. Neurosci. (1)

E. Shtoyerman, A. Arieli, H. Slovin, I. Vanzetta, and A. Grinvald, “Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys,” J. Neurosci. 20(21), 8111–8121 (2000).
[PubMed]

Nat. Methods (3)

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Methods 5(11), 935–938 (2008).
[Crossref] [PubMed]

P. J. Drew, A. Y. Shih, J. D. Driscoll, P. M. Knutsen, P. Blinder, D. Davalos, K. Akassoglou, P. S. Tsai, and D. Kleinfeld, “Chronic optical access through a polished and reinforced thinned skull,” Nat. Methods 7(12), 981–984 (2010).
[Crossref] [PubMed]

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Nat. Neurosci. (1)

T. A. Szuts, V. Fadeyev, S. Kachiguine, A. Sher, M. V. Grivich, M. Agrochão, P. Hottowy, W. Dabrowski, E. V. Lubenov, A. G. Siapas, N. Uchida, A. M. Litke, and M. Meister, “A wireless multi-channel neural amplifier for freely moving animals,” Nat. Neurosci. 14(2), 263–269 (2011).
[Crossref] [PubMed]

Nat. Protoc. (1)

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. A. Lee, R. Mostany, T. D. Mrsic-Flogel, E. Nedivi, C. Portera-Cailliau, K. Svoboda, J. T. Trachtenberg, and L. Wilbrecht, “Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window,” Nat. Protoc. 4(8), 1128–1144 (2009).
[Crossref] [PubMed]

Nat. Rev. Neurosci. (2)

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[Crossref] [PubMed]

K. M. Tye and K. Deisseroth, “Optogenetic investigation of neural circuits underlying brain disease in animal models,” Nat. Rev. Neurosci. 13(4), 251–266 (2012).
[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(6095), 361–364 (1986).
[Crossref] [PubMed]

Neuron (4)

C. M. Niell and M. P. Stryker, “Modulation of visual responses by behavioral state in mouse visual cortex,” Neuron 65(4), 472–479 (2010).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

A. K. Lee, I. D. Manns, B. Sakmann, and M. Brecht, “Whole-cell recordings in freely moving rats,” Neuron 51(4), 399–407 (2006).
[Crossref] [PubMed]

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Neurosurg. Focus (1)

N. Pouratian, A. F. Cannestra, N. A. Martin, and A. W. Toga, “Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping,” Neurosurg. Focus 13(4), e1 (2002).
[Crossref] [PubMed]

Opt. Express (2)

Opt. Lett. (3)

Proc. Natl. Acad. Sci. U.S.A. (1)

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. D. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Science (1)

J. W. Lichtman and W. Denk, “The big and the small: challenges of imaging the brain’s circuits,” Science 334(6056), 618–623 (2011).
[Crossref] [PubMed]

Other (1)

K. Murari, R. Etienne-Cummings, G. Cauwenberghs, and N. Thakor, “An integrated imaging microscope for untethered cortical imaging in freely-moving animals,” in Proceedings of 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology (EMBC,2010), pp. 5795–5798.
[Crossref]

Supplementary Material (1)

NameDescription
» Visualization 1: AVI (7872 KB)      In the movie, rats wearing the micro-imager behaved in a truly free moving status, like rubbing face, eating, running, tracking and climbing.

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Figures (7)

Fig. 1
Fig. 1 The proposed standard alone micro-imager (a) and its design diagram (b): (i) Imaging Module (IM), (ii) Control and Storage Module (CSM), (iii) Powering and Light Module (PLM).
Fig. 2
Fig. 2 The stand-alone micro-imager is wearable (a) and feasible for imaging rat’s brain activities when freely moving in the open field (b). Also, see the supplementary video (Visualization 1).
Fig. 3
Fig. 3 The cranial window preparation for chronic wide-field imaging using contact lens: (a) cranial window on day 0; (b) cranial window after three weeks.
Fig. 4
Fig. 4 Wide-field imaging of brain activities in freely moving status: (a) the OIS image, (b) the contrast image. In (a), the inserted brain phantom shows the imaging window (black box). Two vessels (marked in blue and magenta) and parenchyma area (marked in red) are selected for further analysis. In (b), the supplying artery (marked in black) of the motor cortex and surrounding parenchyma area (marked in gray) are selected as ROIs. Gray bar represents the gray levels in (a), and the color bar represents the contrast values in (b).
Fig. 5
Fig. 5 Chronic monitoring the contrast signals (a) and OIS signals (b) at the selected ROIs (marked in Fig. 4(a)) when the rats were freely moving in the open-field.
Fig. 6
Fig. 6 Changes of rCBF and rHbT when the rats were climbing on the wall. (a) and (b) shows the rCBF and rHbT activities of the ROIs (marked in Fig. 4(b)) in one climbing session. (c) and (d) demonstrate the statistical analysis of the rCBF and rHbT in all 20 climbing sessions on day 0 and day 20 (* indicates a significant difference with p<0.01).
Fig. 7
Fig. 7 The signal crosstalk of the micro-imager in simultaneous LSCI and OIS imaging.

Equations (5)

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

rHbT( x,y,t )=( 1/ εD )ln[ I OIS ( x,y,0 )/ I OIS ( x,y,t ) ]
K s = σ s I
K s 2 =β{ τ c T + τ c 2 2 T 2 [exp( 2T τ c )1]}
τ c 1/v
rCBF= v( t ) v( 0 ) = τ c ( 0 ) τ c ( t )

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