Abstract

Rapid and high-resolution imaging of large tissues is essential in biological research, like brain neuron connectivity research and cancer margins imaging. Here a novel stage-scanning confocal microscopy was developed for rapid imaging of large tissues. Line scanning methods and strip imaging strategy were used to increase the imaging speed. The scientific CMOS was used as line detector in sub-array mode and the optical sectioning ability can be easily adjusted by changing the number of line detectors according to different samples. Fluorescent beads imaging showed resolutions of 0.47 μm, 0.56 μm, and 1.56 μm in the X, Y, and Z directions, respectively, with a 40 × objective lens. A 10 × 10 mm2 coronal plane with enough signal intensity could be imaged in about 88 sec at a sampling resolution of 0.16 μm/pixel. Rapid imaging of mouse brain slices demonstrated the applicability of this system in visualizing neuronal details at high frame rate.

© 2015 Optical Society of America

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References

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2014 (1)

2013 (3)

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

2012 (3)

S. Deng, L. Liu, Z. Liu, Z. Shen, G. Li, and Y. He, “Line-scanning Raman imaging spectroscopy for detection of fingerprints,” Appl. Opt. 51(17), 3701–3706 (2012).
[Crossref] [PubMed]

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

2011 (1)

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

2009 (1)

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

2007 (3)

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

2006 (1)

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[Crossref] [PubMed]

2005 (1)

2003 (1)

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin. Experiment. Ophthalmol. 31(3), 241–245 (2003).
[Crossref] [PubMed]

1999 (1)

1998 (1)

C. J. R. Sheppard and X. Q. Mao, “Confocal microscopes with slit apertures,” J. Mod. Opt. 25, 1169 (1998).

1988 (1)

G. Q. Xiao, T. R. Corle, and G. S. Kino, “Real-time confocal scanning optical microscope,” Appl. Phys. Lett. 53(8), 716–718 (1988).
[Crossref]

Abeytunge, S.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

Anderson, R. R.

Aranda, I.

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

Arganda-Carreras, I.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Bahlmann, K.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Brown, J. Q.

Callaway, E. S.

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

Carlson, A. L.

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

Chapkin, R. S.

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

Coghlan, L. G.

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

Corle, T. R.

G. Q. Xiao, T. R. Corle, and G. S. Kino, “Real-time confocal scanning optical microscope,” Appl. Phys. Lett. 53(8), 716–718 (1988).
[Crossref]

Cushion, J.

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin. Experiment. Ophthalmol. 31(3), 241–245 (2003).
[Crossref] [PubMed]

Deng, S.

Ding, W.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Dorval, T.

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

Dusch, E.

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

Elfer, K. N.

Feng, Z.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

Gareau, D. S.

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Genovesio, A.

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

Gillenwater, A. M.

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

Gong, H.

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

Halpern, A. C.

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

Han, S.

He, Y.

Hu, B.

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

Im, K. B.

Jiang, T.

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

Kadiri, L. R.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Kempe, M.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[Crossref] [PubMed]

Kim, B. M.

Kim, D.

Kim, Y.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Kino, G. S.

G. Q. Xiao, T. R. Corle, and G. S. Kino, “Real-time confocal scanning optical microscope,” Appl. Phys. Lett. 53(8), 716–718 (1988).
[Crossref]

Larson, B.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

Li, A.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

Li, G.

Li, S.

Li, Y.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

Liu, L.

Liu, Z.

Luo, Q.

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Lv, X.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

Maitland, K. C.

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

Mao, X. Q.

C. J. R. Sheppard and X. Q. Mao, “Confocal microscopes with slit apertures,” J. Mod. Opt. 25, 1169 (1998).

Nehal, K. S.

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

Olsovsky, C. A.

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

Osten, P.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Park, H.

Patel, Y. G.

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

Patterson, B. A.

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin. Experiment. Ophthalmol. 31(3), 241–245 (2003).
[Crossref] [PubMed]

Qi, X.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

Ragan, T.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Rajadhyaksha, M.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, “Video-rate confocal scanning laser microscope for imaging human tissues in vivo,” Appl. Opt. 38(10), 2105–2115 (1999).
[Crossref] [PubMed]

Reinholz, F. N.

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin. Experiment. Ophthalmol. 31(3), 241–245 (2003).
[Crossref] [PubMed]

Richards-Kortum, R. R.

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

Saldua, M. A.

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

Schlichenmeyer, T. C.

Seung, H. S.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Shen, Z.

Sheppard, C. J. R.

C. J. R. Sheppard and X. Q. Mao, “Confocal microscopes with slit apertures,” J. Mod. Opt. 25, 1169 (1998).

Sutin, J.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Taranda, J.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Toledo-Crow, R.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

Venkataraju, K. U.

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Vincent, N.

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

Wachsmuth, M.

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

Wang, M.

Wang, X.

Webb, R. H.

Wolleschensky, R.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[Crossref] [PubMed]

Wu, J.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Xiao, G. Q.

G. Q. Xiao, T. R. Corle, and G. S. Kino, “Real-time confocal scanning optical microscope,” Appl. Phys. Lett. 53(8), 716–718 (1988).
[Crossref]

Xu, D.

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

Xu, T.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Yan, C.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Yang, Z.

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

Zeng, S.

T. Zheng, Z. Yang, A. Li, X. Lv, Z. Zhou, X. Wang, X. Qi, S. Li, Q. Luo, H. Gong, and S. Zeng, “Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography,” Opt. Express 21(8), 9839–9850 (2013).
[Crossref] [PubMed]

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

Zheng, T.

Zhou, Z.

Zimmermann, B.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[Crossref] [PubMed]

Appl. Opt. (2)

Appl. Phys. Lett. (1)

G. Q. Xiao, T. R. Corle, and G. S. Kino, “Real-time confocal scanning optical microscope,” Appl. Phys. Lett. 53(8), 716–718 (1988).
[Crossref]

Biomed. Opt. Express (1)

Clin. Experiment. Ophthalmol. (1)

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin. Experiment. Ophthalmol. 31(3), 241–245 (2003).
[Crossref] [PubMed]

J. Biomed. Opt. (5)

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[Crossref] [PubMed]

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[Crossref] [PubMed]

D. Xu, T. Jiang, A. Li, B. Hu, Z. Feng, H. Gong, S. Zeng, and Q. Luo, “Fast optical sectioning obtained by structured illumination microscopy using a digital mirror device,” J. Biomed. Opt. 18(6), 060503 (2013).
[Crossref] [PubMed]

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt. 16(5), 050504 (2011).
[Crossref] [PubMed]

M. A. Saldua, C. A. Olsovsky, E. S. Callaway, R. S. Chapkin, and K. C. Maitland, “Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope,” J. Biomed. Opt. 17(1), 016006 (2012).
[Crossref] [PubMed]

J. Microsc. (3)

E. Dusch, T. Dorval, N. Vincent, M. Wachsmuth, and A. Genovesio, “Three-dimensional point spread function model for line-scanning confocal microscope with high-aperture objective,” J. Microsc. 228(2), 132–138 (2007).
[Crossref] [PubMed]

D. S. Gareau, Y. G. Patel, Y. Li, I. Aranda, A. C. Halpern, K. S. Nehal, and M. Rajadhyaksha, “Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology,” J. Microsc. 233(1), 149–159 (2009).
[Crossref] [PubMed]

A. L. Carlson, L. G. Coghlan, A. M. Gillenwater, and R. R. Richards-Kortum, “Dual-mode reflectance and fluorescence near-video-rate confocal microscope for architectural, morphological and molecular imaging of tissue,” J. Microsc. 228(1), 11–24 (2007).
[Crossref] [PubMed]

J. Mod. Opt. (1)

C. J. R. Sheppard and X. Q. Mao, “Confocal microscopes with slit apertures,” J. Mod. Opt. 25, 1169 (1998).

Nat. Methods (1)

T. Ragan, L. R. Kadiri, K. U. Venkataraju, K. Bahlmann, J. Sutin, J. Taranda, I. Arganda-Carreras, Y. Kim, H. S. Seung, and P. Osten, “Serial two-photon tomography for automated ex vivo mouse brain imaging,” Nat. Methods 9(3), 255–258 (2012).
[Crossref] [PubMed]

Neuroimage (1)

H. Gong, S. Zeng, C. Yan, X. Lv, Z. Yang, T. Xu, Z. Feng, W. Ding, X. Qi, A. Li, J. Wu, and Q. Luo, “Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution,” Neuroimage 74, 87–98 (2013).
[Crossref] [PubMed]

Opt. Express (2)

Other (1)

J. B. Pawley and R. B. R. Masters, “Handbook of Biological Confocal Microscopy, Second Edition,” OPTICE 35, 2765–2766 (1996).

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Figures (6)

Fig. 1
Fig. 1 (a) Schematic configuration of the stage-scanning microscope. A diffraction-limited illumination line was provided on the sample by an optical system. (b) Schematic representation of the method for specimen imaging. (c) Schematic representation of the strategy of large tissue imaging.
Fig. 2
Fig. 2 Signal to noise ratios obtained using varying number of line detectors. A 40 × , 0.8 NA water objective lens was used. Widths of 1, 2, 4, 6, and 8 lines correspond to 0.22, 0.44, 0.88, 1.32, and 1.76 AU. Data represent the mean ± standard deviation of results obtained in 5 different fluorescent beads.
Fig. 3
Fig. 3 Measurement of the lateral and axial point spread function. (a) Lateral normalized intensity distribution of fluorescent beads. Red line represents Gaussian fit in X direction and blue line represents Gaussian fit in Y direction. The FWHM in X and Y directions are 0.47 μm ± 0.02 μm and 0.56 μm ± 0.01 μm(n = 5), respectively. (b) Axial normalized intensity distribution of fluorescent beads. Green line represents Gaussian fit. The FWHM in Z direction is 1.56 μm ± 0.05 μm (n = 5).
Fig. 4
Fig. 4 Imaging of a 50-μm-thick brain slice. (a) Image recorded using the stage-scanning confocal system. The visual slit width is 4 lines. (b) Image recorded using the wide-field image system. (c) The normalized intensity curve along the line in (a) and (b). Scale bar, 10 μm.
Fig. 5
Fig. 5 (a) Maximum intensity projection of 45μm z-stack. Scale bar: 50μm. (b) (c) Enlarged images which were marked as red box in (a). Scale bar: 10μm.
Fig. 6
Fig. 6 Imaging of a large area mouse brain slice. (a) The imaged region is about 1.628 mm wide and 3.328 mm long. Scale bar: 500 μm. (b) (c) (d) (e) Enlarged images of brain regions marked as red box in (a). The enlarged images demonstrate visualization of dendrites spine, buttons, and axon fibers in the whole imaging regions. Scale bar, 20 μm.

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