Abstract

Surgical procedures as a prelude to optical imaging are a rate-limiting step in experimental neuroscience. Towards automation of these procedures, we describe the use of nonlinear optical techniques to create a thinned skull window for transcranial imaging. Metrology by second harmonic generation was used to map the surfaces of the skull and define a cutting path. Plasma-mediated laser ablation was utilized to cut bone. Mice prepared with these techniques were used to image subsurface cortical vasculature and blood flow. The viability of the brain tissue was confirmed via histological analysis and supports the utility of solely optical techniques for osteotomy and potentially other surgical procedures.

© 2013 OSA

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    [CrossRef]

2012

D. C. Jeong, P. S. Tsai, and D. Kleinfeld, “Prospect for feedback guided surgery with ultra-short pulsed laser light,” Curr. Opin. Neurobiol.22(1), 24–33 (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]

J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
[CrossRef]

A. N. Zorzos, J. Scholvin, E. S. Boyden, and C. G. Fonstad, “Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits,” Opt. Lett.37(23), 4841–4843 (2012).
[CrossRef] [PubMed]

2010

D. N. Vitek, D. E. Adams, A. Johnson, P. S. Tsai, S. Backus, C. G. Durfee, D. Kleinfeld, and J. A. Squier, “Temporally focused femtosecond laser pulses for low numerical aperture micromachining through optically transparent materials,” Opt. Express18(17), 18086–18094 (2010).
[CrossRef] [PubMed]

P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

M. Farid and R. F. Steinert, “Femtosecond laser-assisted corneal surgery,” Curr. Opin. Ophthalmol.21(4), 288–292 (2010).
[PubMed]

2009

S. H. Chung and E. Mazur, “Surgical applications of femtosecond lasers,” J Biophotonics2(10), 557–572 (2009).
[CrossRef] [PubMed]

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
[CrossRef] [PubMed]

2008

2007

E. L. Gurevich and R. Hergenröder, “Femtosecond laser-induced breakdown spectroscopy: Physics, applications, and perspectives,” Appl. Spectrosc.61(10), 233A–242A (2007).
[CrossRef] [PubMed]

Y. Liu and M. Niemz, “Ablation of femural bone with femtosecond laser pulses--A feasibility study,” Lasers Med. Sci.22(3), 171–174 (2007).
[CrossRef] [PubMed]

H. T. Xu, F. Pan, G. Yang, and W. B. Gan, “Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex,” Nat. Neurosci.10(5), 549–551 (2007).
[CrossRef] [PubMed]

S. I. Mian and R. M. Shtein, “Femtosecond laser-assisted corneal surgery,” Curr. Opin. Ophthalmol.18(4), 295–299 (2007).
[CrossRef] [PubMed]

2006

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
[CrossRef] [PubMed]

2005

H. K. Soong, S. Mian, O. Abbasi, and T. Juhasz, “Femtosecond laser-assisted posterior lamellar keratoplasty: Initial studies of surgical technique in eye bank eyes,” Ophthalmology112(1), 44–49 (2005).
[CrossRef] [PubMed]

B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods2(12), 932–940 (2005).
[CrossRef] [PubMed]

D. Oron and Y. Silberberg, “Spatiotemporal coherent control using shaped, temporally focused pulses,” Opt. Express13(24), 9903–9908 (2005).
[CrossRef] [PubMed]

2004

A. P. Joglekar, H. H. Liu, E. Meyhöfer, G. Mourou, and A. J. Hunt, “Optics at critical intensity: Applications to nanomorphing,” Proc. Natl. Acad. Sci. U.S.A.101(16), 5856–5861 (2004).
[CrossRef] [PubMed]

2003

A. Vogel and V. Venugopalan, “Mechanisms of pulsed laser ablation of biological tissues,” Chem. Rev.103(2), 577–644 (2003).
[CrossRef] [PubMed]

P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
[CrossRef] [PubMed]

2002

W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
[CrossRef] [PubMed]

A. Arieli, A. Grinvald, and H. Slovin, “Dural substitute for long-term imaging of cortical activity in behaving monkeys and its clinical implications,” J. Neurosci. Methods114(2), 119–133 (2002).
[CrossRef] [PubMed]

C. B. Schaffer, N. Nishimura, E. N. Glezer, A. M. T. Kim, and E. Mazur, “Dynamics of femtosecond laser-induced breakdown in water from femtoseconds to microseconds,” Opt. Express10(3), 196–203 (2002).
[CrossRef] [PubMed]

1999

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J.77(6), 3341–3349 (1999).
[CrossRef] [PubMed]

1998

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

B. M. Kim, M. D. Feit, A. M. Rubenchik, B. M. Mammini, and L. B. Da Silva, “Optical feedback signal for ultrashort laser-pulse ablation of tissue,” Appl. Surf. Sci.127–129, 857–862 (1998).
[CrossRef]

1997

Y. Guo, P. P. Ho, H. Savage, D. Harris, P. Sacks, S. Schantz, F. Liu, N. Zhadin, and R. R. Alfano, “Second-harmonic tomography of tissues,” Opt. Lett.22(17), 1323–1325 (1997).
[CrossRef] [PubMed]

E. M. Maynard, C. T. Nordhausen, and R. A. Normann, “The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces,” Electroencephalogr. Clin. Neurophysiol.102(3), 228–239 (1997).
[CrossRef] [PubMed]

K. Svoboda, W. Denk, D. Kleinfeld, and D. W. Tank, “In vivo dendritic calcium dynamics in neocortical pyramidal neurons,” Nature385(6612), 161–165 (1997).
[CrossRef] [PubMed]

1996

D. A. Dawson and J. M. Hallenbeck, “Acute focal ischemia-induced alterations in MAP2 immunostaining: Description of temporal changes and utilization as a marker for volumetric assessment of acute brain injury,” J. Cereb. Blood Flow Metab.16(1), 170–174 (1996).
[CrossRef] [PubMed]

J. E. W. Mayhew, S. Askew, Y. Zheng, J. Porrill, G. W. M. Westby, P. Redgrave, D. M. Rector, and R. M. Harper, “Cerebral vasomotion: 0.1 Hz oscillation in reflectance imaging of neural activity,” Neuroimage4(3), 183–193 (1996).
[CrossRef] [PubMed]

F. H. Loesel, M. H. Niemz, J. F. Bille, and T. Juhasz, “Laser-induced optical breakdown on hard and soft tissues and its dependence on the pulse duration: Experiment and model,” IEEE J. Quantum Electron.32(10), 1717–1722 (1996).
[CrossRef]

1995

B. C. Stuart, M. D. Feit, A. M. Rubenchik, B. W. Shore, and M. D. Perry, “Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses,” Phys. Rev. Lett.74(12), 2248–2251 (1995).
[CrossRef] [PubMed]

1992

R. J. Mullen, C. R. Buck, and A. M. Smith, “NeuN, a neuronal specific nuclear protein in vertebrates,” Development116(1), 201–211 (1992).
[PubMed]

1991

R. D. Piper, G. A. Lambert, and J. W. Duckworth, “Cortical blood flow changes during spreading depression in cats,” Am. J. Physiol.261(1 Pt 2), H96–H102 (1991).
[PubMed]

1990

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1979

N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
[CrossRef] [PubMed]

1962

R. W. Terhune, P. D. Maker, and C. M. Savage, “Optical harmonic generation in calcite,” Phys. Rev. Lett.8(10), 404–406 (1962).
[CrossRef]

Abbasi, O.

H. K. Soong, S. Mian, O. Abbasi, and T. Juhasz, “Femtosecond laser-assisted posterior lamellar keratoplasty: Initial studies of surgical technique in eye bank eyes,” Ophthalmology112(1), 44–49 (2005).
[CrossRef] [PubMed]

Adams, D. E.

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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Alfano, R. R.

Arieli, A.

A. Arieli, A. Grinvald, and H. Slovin, “Dural substitute for long-term imaging of cortical activity in behaving monkeys and its clinical implications,” J. Neurosci. Methods114(2), 119–133 (2002).
[CrossRef] [PubMed]

Armstrong, W. B.

W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
[CrossRef] [PubMed]

Askew, S.

J. E. W. Mayhew, S. Askew, Y. Zheng, J. Porrill, G. W. M. Westby, P. Redgrave, D. M. Rector, and R. M. Harper, “Cerebral vasomotion: 0.1 Hz oscillation in reflectance imaging of neural activity,” Neuroimage4(3), 183–193 (1996).
[CrossRef] [PubMed]

Backus, S.

Bille, J. F.

F. H. Loesel, M. H. Niemz, J. F. Bille, and T. Juhasz, “Laser-induced optical breakdown on hard and soft tissues and its dependence on the pulse duration: Experiment and model,” IEEE J. Quantum Electron.32(10), 1717–1722 (1996).
[CrossRef]

Blinder, P.

P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
[CrossRef] [PubMed]

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. 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]

Boyden, E. S.

Buchfelder, M.

B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
[CrossRef] [PubMed]

Buck, C. R.

R. J. Mullen, C. R. Buck, and A. M. Smith, “NeuN, a neuronal specific nuclear protein in vertebrates,” Development116(1), 201–211 (1992).
[PubMed]

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Carriles, R.

Cauwenberghs, G.

P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (2010).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
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W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
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B. M. Kim, M. D. Feit, A. M. Rubenchik, B. M. Mammini, and L. B. Da Silva, “Optical feedback signal for ultrashort laser-pulse ablation of tissue,” Appl. Surf. Sci.127–129, 857–862 (1998).
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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. Methods7(12), 981–984 (2010).
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D. A. Dawson and J. M. Hallenbeck, “Acute focal ischemia-induced alterations in MAP2 immunostaining: Description of temporal changes and utilization as a marker for volumetric assessment of acute brain injury,” J. Cereb. Blood Flow Metab.16(1), 170–174 (1996).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
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F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods2(12), 932–940 (2005).
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D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998).
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K. Svoboda, W. Denk, D. Kleinfeld, and D. W. Tank, “In vivo dendritic calcium dynamics in neocortical pyramidal neurons,” Nature385(6612), 161–165 (1997).
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W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
[CrossRef]

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]

P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Driscoll, J. D.

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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Duckworth, J. W.

R. D. Piper, G. A. Lambert, and J. W. Duckworth, “Cortical blood flow changes during spreading depression in cats,” Am. J. Physiol.261(1 Pt 2), H96–H102 (1991).
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B. M. Kim, M. D. Feit, A. M. Rubenchik, B. M. Mammini, and L. B. Da Silva, “Optical feedback signal for ultrashort laser-pulse ablation of tissue,” Appl. Surf. Sci.127–129, 857–862 (1998).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
[CrossRef]

Fonstad, C. G.

Friedman, B.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
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P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
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H. T. Xu, F. Pan, G. Yang, and W. B. Gan, “Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex,” Nat. Neurosci.10(5), 549–551 (2007).
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B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
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Guo, Y.

Gurevich, E. L.

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D. A. Dawson and J. M. Hallenbeck, “Acute focal ischemia-induced alterations in MAP2 immunostaining: Description of temporal changes and utilization as a marker for volumetric assessment of acute brain injury,” J. Cereb. Blood Flow Metab.16(1), 170–174 (1996).
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Harper, R. M.

J. E. W. Mayhew, S. Askew, Y. Zheng, J. Porrill, G. W. M. Westby, P. Redgrave, D. M. Rector, and R. M. Harper, “Cerebral vasomotion: 0.1 Hz oscillation in reflectance imaging of neural activity,” Neuroimage4(3), 183–193 (1996).
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Harris, D.

Helmchen, F.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods2(12), 932–940 (2005).
[CrossRef] [PubMed]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

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Ho, P. P.

Hofer, S. B.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Holtmaat, A.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Hoover, E. E.

J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
[CrossRef]

K. E. Sheetz, E. E. Hoover, R. Carriles, D. Kleinfeld, and J. A. Squier, “Advancing multifocal nonlinear microscopy: Development and application of a novel multibeam Yb:KGd(WO4)2 oscillator,” Opt. Express16(22), 17574–17584 (2008).
[CrossRef] [PubMed]

Hübener, M.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Hunt, A. J.

A. P. Joglekar, H. H. Liu, E. Meyhöfer, G. Mourou, and A. J. Hunt, “Optics at critical intensity: Applications to nanomorphing,” Proc. Natl. Acad. Sci. U.S.A.101(16), 5856–5861 (2004).
[CrossRef] [PubMed]

Ifarraguerri, A. I.

P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
[CrossRef] [PubMed]

Jeong, D. C.

D. C. Jeong, P. S. Tsai, and D. Kleinfeld, “Prospect for feedback guided surgery with ultra-short pulsed laser light,” Curr. Opin. Neurobiol.22(1), 24–33 (2012).
[CrossRef] [PubMed]

Jin, Y.

P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
[CrossRef] [PubMed]

Joglekar, A. P.

A. P. Joglekar, H. H. Liu, E. Meyhöfer, G. Mourou, and A. J. Hunt, “Optics at critical intensity: Applications to nanomorphing,” Proc. Natl. Acad. Sci. U.S.A.101(16), 5856–5861 (2004).
[CrossRef] [PubMed]

Johnson, A.

Johnson, W. G.

N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
[CrossRef] [PubMed]

Juhasz, T.

H. K. Soong, S. Mian, O. Abbasi, and T. Juhasz, “Femtosecond laser-assisted posterior lamellar keratoplasty: Initial studies of surgical technique in eye bank eyes,” Ophthalmology112(1), 44–49 (2005).
[CrossRef] [PubMed]

F. H. Loesel, M. H. Niemz, J. F. Bille, and T. Juhasz, “Laser-induced optical breakdown on hard and soft tissues and its dependence on the pulse duration: Experiment and model,” IEEE J. Quantum Electron.32(10), 1717–1722 (1996).
[CrossRef]

Keck, T.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Kim, A. M. T.

Kim, B. M.

B. M. Kim, M. D. Feit, A. M. Rubenchik, B. M. Mammini, and L. B. Da Silva, “Optical feedback signal for ultrashort laser-pulse ablation of tissue,” Appl. Surf. Sci.127–129, 857–862 (1998).
[CrossRef]

Kleinfeld, D.

J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
[CrossRef]

D. C. Jeong, P. S. Tsai, and D. Kleinfeld, “Prospect for feedback guided surgery with ultra-short pulsed laser light,” Curr. Opin. Neurobiol.22(1), 24–33 (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]

P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

D. N. Vitek, D. E. Adams, A. Johnson, P. S. Tsai, S. Backus, C. G. Durfee, D. Kleinfeld, and J. A. Squier, “Temporally focused femtosecond laser pulses for low numerical aperture micromachining through optically transparent materials,” Opt. Express18(17), 18086–18094 (2010).
[CrossRef] [PubMed]

P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
[CrossRef] [PubMed]

K. E. Sheetz, E. E. Hoover, R. Carriles, D. Kleinfeld, and J. A. Squier, “Advancing multifocal nonlinear microscopy: Development and application of a novel multibeam Yb:KGd(WO4)2 oscillator,” Opt. Express16(22), 17574–17584 (2008).
[CrossRef] [PubMed]

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
[CrossRef] [PubMed]

P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
[CrossRef] [PubMed]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

K. Svoboda, W. Denk, D. Kleinfeld, and D. W. Tank, “In vivo dendritic calcium dynamics in neocortical pyramidal neurons,” Nature385(6612), 161–165 (1997).
[CrossRef] [PubMed]

Knott, G.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Knutsen, P. M.

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. Methods7(12), 981–984 (2010).
[CrossRef] [PubMed]

Kruschat, T. M. A.

B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
[CrossRef] [PubMed]

Lambert, G. A.

R. D. Piper, G. A. Lambert, and J. W. Duckworth, “Cortical blood flow changes during spreading depression in cats,” Am. J. Physiol.261(1 Pt 2), H96–H102 (1991).
[PubMed]

Latov, N.

N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
[CrossRef] [PubMed]

Lee, W. C.

A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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]

Lev-Ram, V.

P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
[CrossRef] [PubMed]

Lewis, A.

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J.77(6), 3341–3349 (1999).
[CrossRef] [PubMed]

Liu, F.

Liu, H. H.

A. P. Joglekar, H. H. Liu, E. Meyhöfer, G. Mourou, and A. J. Hunt, “Optics at critical intensity: Applications to nanomorphing,” Proc. Natl. Acad. Sci. U.S.A.101(16), 5856–5861 (2004).
[CrossRef] [PubMed]

Liu, Y.

Y. Liu and M. Niemz, “Ablation of femural bone with femtosecond laser pulses--A feasibility study,” Lasers Med. Sci.22(3), 171–174 (2007).
[CrossRef] [PubMed]

Loesel, F. H.

F. H. Loesel, M. H. Niemz, J. F. Bille, and T. Juhasz, “Laser-induced optical breakdown on hard and soft tissues and its dependence on the pulse duration: Experiment and model,” IEEE J. Quantum Electron.32(10), 1717–1722 (1996).
[CrossRef]

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P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J.77(6), 3341–3349 (1999).
[CrossRef] [PubMed]

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B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
[CrossRef] [PubMed]

Lyden, P. D.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
[CrossRef] [PubMed]

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R. W. Terhune, P. D. Maker, and C. M. Savage, “Optical harmonic generation in calcite,” Phys. Rev. Lett.8(10), 404–406 (1962).
[CrossRef]

Mammini, B. M.

B. M. Kim, M. D. Feit, A. M. Rubenchik, B. M. Mammini, and L. B. Da Silva, “Optical feedback signal for ultrashort laser-pulse ablation of tissue,” Appl. Surf. Sci.127–129, 857–862 (1998).
[CrossRef]

Mayhew, J. E. W.

J. E. W. Mayhew, S. Askew, Y. Zheng, J. Porrill, G. W. M. Westby, P. Redgrave, D. M. Rector, and R. M. Harper, “Cerebral vasomotion: 0.1 Hz oscillation in reflectance imaging of neural activity,” Neuroimage4(3), 183–193 (1996).
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E. M. Maynard, C. T. Nordhausen, and R. A. Normann, “The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces,” Electroencephalogr. Clin. Neurophysiol.102(3), 228–239 (1997).
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B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
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H. K. Soong, S. Mian, O. Abbasi, and T. Juhasz, “Femtosecond laser-assisted posterior lamellar keratoplasty: Initial studies of surgical technique in eye bank eyes,” Ophthalmology112(1), 44–49 (2005).
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S. I. Mian and R. M. Shtein, “Femtosecond laser-assisted corneal surgery,” Curr. Opin. Ophthalmol.18(4), 295–299 (2007).
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P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
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D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A.95(26), 15741–15746 (1998).
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A. P. Joglekar, H. H. Liu, E. Meyhöfer, G. Mourou, and A. J. Hunt, “Optics at critical intensity: Applications to nanomorphing,” Proc. Natl. Acad. Sci. U.S.A.101(16), 5856–5861 (2004).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
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W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
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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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N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
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C. B. Schaffer, N. Nishimura, E. N. Glezer, A. M. T. Kim, and E. Mazur, “Dynamics of femtosecond laser-induced breakdown in water from femtoseconds to microseconds,” Opt. Express10(3), 196–203 (2002).
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E. M. Maynard, C. T. Nordhausen, and R. A. Normann, “The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces,” Electroencephalogr. Clin. Neurophysiol.102(3), 228–239 (1997).
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E. M. Maynard, C. T. Nordhausen, and R. A. Normann, “The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces,” Electroencephalogr. Clin. Neurophysiol.102(3), 228–239 (1997).
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H. T. Xu, F. Pan, G. Yang, and W. B. Gan, “Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex,” Nat. Neurosci.10(5), 549–551 (2007).
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B. C. Stuart, M. D. Feit, A. M. Rubenchik, B. W. Shore, and M. D. Perry, “Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses,” Phys. Rev. Lett.74(12), 2248–2251 (1995).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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J. E. W. Mayhew, S. Askew, Y. Zheng, J. Porrill, G. W. M. Westby, P. Redgrave, D. M. Rector, and R. M. Harper, “Cerebral vasomotion: 0.1 Hz oscillation in reflectance imaging of neural activity,” Neuroimage4(3), 183–193 (1996).
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W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
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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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N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, “Targeted insult to individual subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke,” Nat. Methods3(2), 99–108 (2006).
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B. J. Schaller, R. Gruber, H. A. Merten, T. M. A. Kruschat, H. M. D. Schliephake, M. Buchfelder, and H. C. Ludwig, “Piezoelectric bone surgery: A revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note,” Neurosurgery57(Suppl.4 ), E410, discussion E410 (2005).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
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K. E. Sheetz, E. E. Hoover, R. Carriles, D. Kleinfeld, and J. A. Squier, “Advancing multifocal nonlinear microscopy: Development and application of a novel multibeam Yb:KGd(WO4)2 oscillator,” Opt. Express16(22), 17574–17584 (2008).
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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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P. J. Drew, P. Blinder, G. Cauwenberghs, A. Y. Shih, and D. Kleinfeld, “Rapid determination of particle velocity from space-time images using the Radon transform,” J. Comput. Neurosci.29(1-2), 5–11 (2010).
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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. Methods7(12), 981–984 (2010).
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B. C. Stuart, M. D. Feit, A. M. Rubenchik, B. W. Shore, and M. D. Perry, “Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses,” Phys. Rev. Lett.74(12), 2248–2251 (1995).
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S. I. Mian and R. M. Shtein, “Femtosecond laser-assisted corneal surgery,” Curr. Opin. Ophthalmol.18(4), 295–299 (2007).
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Silverman, A.-J.

N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A.-J. Silverman, R. Defendini, and L. Cote, “Fibrillary astrocytes proliferate in response to brain injury,” Dev. Biol.72(2), 381–384 (1979).
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R. J. Mullen, C. R. Buck, and A. M. Smith, “NeuN, a neuronal specific nuclear protein in vertebrates,” Development116(1), 201–211 (1992).
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H. K. Soong, S. Mian, O. Abbasi, and T. Juhasz, “Femtosecond laser-assisted posterior lamellar keratoplasty: Initial studies of surgical technique in eye bank eyes,” Ophthalmology112(1), 44–49 (2005).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
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D. N. Vitek, D. E. Adams, A. Johnson, P. S. Tsai, S. Backus, C. G. Durfee, D. Kleinfeld, and J. A. Squier, “Temporally focused femtosecond laser pulses for low numerical aperture micromachining through optically transparent materials,” Opt. Express18(17), 18086–18094 (2010).
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P. S. Tsai, P. Blinder, B. J. Migliori, J. Neev, Y. Jin, J. A. Squier, and D. Kleinfeld, “Plasma-mediated ablation: An optical tool for submicrometer surgery on neuronal and vascular systems,” Curr. Opin. Biotechnol.20(1), 90–99 (2009).
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W. B. Armstrong, J. A. Neev, L. B. Da Silva, A. M. Rubenchik, and B. C. Stuart, “Ultrashort pulse laser ossicular ablation and stapedotomy in cadaveric bone,” Lasers Surg. Med.30(3), 216–220 (2002).
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B. C. Stuart, M. D. Feit, A. M. Rubenchik, B. W. Shore, and M. D. Perry, “Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses,” Phys. Rev. Lett.74(12), 2248–2251 (1995).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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K. Svoboda, W. Denk, D. Kleinfeld, and D. W. Tank, “In vivo dendritic calcium dynamics in neocortical pyramidal neurons,” Nature385(6612), 161–165 (1997).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
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K. Svoboda, W. Denk, D. Kleinfeld, and D. W. Tank, “In vivo dendritic calcium dynamics in neocortical pyramidal neurons,” Nature385(6612), 161–165 (1997).
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R. W. Terhune, P. D. Maker, and C. M. Savage, “Optical harmonic generation in calcite,” Phys. Rev. Lett.8(10), 404–406 (1962).
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P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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D. C. Jeong, P. S. Tsai, and D. Kleinfeld, “Prospect for feedback guided surgery with ultra-short pulsed laser light,” Curr. Opin. Neurobiol.22(1), 24–33 (2012).
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A. Holtmaat, T. Bonhoeffer, D. K. Chow, J. Chuckowree, V. De Paola, S. B. Hofer, M. Hübener, T. Keck, G. Knott, W. C. 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).
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P. S. Tsai, B. Friedman, A. I. Ifarraguerri, B. D. Thompson, V. Lev-Ram, C. B. Schaffer, Q. Xiong, R. Y. Tsien, J. A. Squier, and D. Kleinfeld, “All-optical histology using ultrashort laser pulses,” Neuron39(1), 27–41 (2003).
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H. T. Xu, F. Pan, G. Yang, and W. B. Gan, “Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex,” Nat. Neurosci.10(5), 549–551 (2007).
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H. T. Xu, F. Pan, G. Yang, and W. B. Gan, “Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex,” Nat. Neurosci.10(5), 549–551 (2007).
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J. J. Field, K. E. Sheetz, E. V. Chandler, E. E. Hoover, M. D. Young, S.-Y. Ding, A. W. Sylvester, D. Kleinfeld, and J. A. Squier, “Differential multiphoton laser-scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.18(1), 14–28 (2012).
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Figures (5)

Fig. 1
Fig. 1

Flow chart and schematic of the experimental set-up. (a) Procedures to produce a thinned skull window for transcranial imaging in mice. (b) Schematic of the set-up. An ultrashort pulsed Ti-sapphire oscillator (Mira HP pumped by a Verdi V18; Coherent, Inc.) is used for metrology of the skull based on the detection (H7422-40; Hamamatsu) of second harmonic light. A Ti-sapphire regeneratively amplified laser system (Libra, Coherent Inc.) is used as the source for the laser ablation. The two beams share the optical axis and are merged with a polarizing beam splitter placed before the water dipping objective (LUMPLANFL IR 40X 0.80 NA; Olympus). Translational stages (XYR-6060; Danaher) were used to scan incoming optical beam in X- and Y-directions. A third stage was used to move the preparation along the optical axis, i.e., Z-direction (LMB-600; Danaher). The intensity of the metrology and ablation laser beams were controlled with half-wave plates followed by a polarizing beam splitter; the plates were coupled to a stepper motor and rotated for the desired intensity. The entire procedure is under control of a computer algorithm that operated the shutters (LS3; Uniblitz) and the stage controller (DMC-4040; Galil) and synchronized the data acquisition (NI 6110; National Instruments).

Fig. 2
Fig. 2

Height and thickness of the skull as measured via second harmonic generation. (a) Intact bone was scanned along the Z-direction with ultrashort pulsed laser light. The signal rapidly increased as the focus approached the surface of the skull. (b) Map of height versus medial-lateral position for a band across the skull. (c) Overlay of the curvature obtained in panel b with a wide-field fluorescent image of a cross-section of the skull. The section was obtained by mechanically cutting the skull along the previous scanned path.

Fig. 3
Fig. 3

Creation of a thinned skull by plasma-mediated laser ablation. (a) The intrinsic curvature of the skull was mapped over a 2 mm by 2 mm area with SHG metrology. (b) A smoothed version of the data in panel a that was used to to calculate translational stage movements and shutter openings for thinning. (c) The decay in the SHG signal when the skull has been cut to within a thickness of 50 µm. Note the sharp fall-off in SHG signal at the interior surface of the skull compared with the signal from a thick skull (Fig. 2(a)). (d) The top surface of the thinned skull window measured with SHG metrology after completion of the ablation process. (e) Photomicrograph of the surface in panel d. (f) Histogram of the thickness obtained from measurements in panel d show the distribution of thicnesses; the points marked “Edges” are at the border of the window.

Fig. 4
Fig. 4

In vivo two-photon laser scanning imaging demonstrates the utility of a laser ablated thinned skull window for functional imaging in mice. The blood plasma was stained with a high-molecular weight fluorescein-labeled dextran (2 MDa; Sigma). The window is above parietal cortex. (a) Maximum projection of a stack of images from a depth of 50 µm to 100um below the pia. The imaged area is 300 µm by 300 µm. (b) The same field as in panel a with a projection from 100 µm to 150 µm below the pia. (c) The stacks used for panels a and b were resliced to visualize the vessels along the optical axis. Note the penetrating vessels and fine microvessels. (d) A single microvessel that lies within the focal plane at a depth of 40 µm below the pia. The scan path lies along a straight section of the vessel that is used to track red blood cell flow. (e) Line-scan data from successive scans through the vessel in panel d. Individual red blood cells appear as dark streaks against the fluorescent blood plasma. The velocity of the flow is inversely proportional to the slope of the streaks. (f) Spectral power of the time series of the RBC speed in a vessel, located 80 µm below the pia, shows low frequency vasomotion broadly centred near 0.2 Hz and the heart rate at 8 Hz.

Fig. 5
Fig. 5

Immunological assays of the viability of parietal cortex after laser ablation to create a transcranial window and functional imaging through the window. Alternate brain sections were stained with immunological markers to detect possible damage from the laser ablation and imaging. (a) Staining for reactive astrocytes with α-GFAP visualized with a fluorescent secondary antibody. The tissue under the thinned skull window had α-GFAP levels comparable to the contralateral control side. (b) Staining for the pan-neuronal marker α-NeuN, which lables essentially all neuronal nuclei. Both the window and control sides have comparable neuronal cell densities. (c) Staining for microtubules, as a test of neuronal integrity, with α-MAP. The processes of the neurons are preserved for both the window and control sides of the section.

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