Abstract

One critical challenge in studying neural circuits of freely behaving model organisms is to record neural signals distributed within the whole brain, yet simultaneously maintaining cellular resolution. However, due to the dense packing of neuron cells in animal brains, high numerical aperture (NA) objectives are often required to differentiate neighboring neurons with the consequent need for axial scanning for whole brain imaging. Extending the depth of focus (EDoF) will be beneficial for fast 3D imaging of those neurons. However, current EDoF-enabled microscopes are primarily based on objectives with small NAs (≤0.3 ) such that the paraxial approximation can be applied. In this paper, we started from a nonparaxial approximation of the defocus aberration and derived a new phase mask that was appropriate for large NA microscopic systems. We validated the performance experimentally with a spatial light modulator (SLM) to create the designed phase mask. The performance was tested on different samples such as multilayered fluorescence beads and thick brain tissues, as well as with different objectives. Results confirmed that our design has extended the depth of focus about 10 fold and the image quality is much higher than those based on the most common EDoF method, the cubic phase method, popularly used to generate Airy beams. Meanwhile, our phase mask is rotationally symmetric and easy to fabricate. We fabricated one such phase plate and tested it on the pan-neuronal labeled Caenorhabditis elegans (C.elegans). The imaging performance demonstrated that we can capture all neurons in the whole brain with one snapshot and with cellular resolution, while the imaging speed is increased about 3 fold compared to the system using SLM. Thus we have shown that our method can not only provide the required imaging speed and resolution for studying neural activities in model animals, but also can be implemented as a low-cost, add-on module that can immediately augment existing fluorescence microscopes with only minor system modifications, and yielding substantially higher photon efficiency than SLM-based methods.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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2019 (1)

2018 (2)

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

B. Cai, X. Zhai, Z. Wang, Y. Shen, R. Xu, Z. J. Smith, Q. Wen, and K. Chu, “Optical volumetric projection for fast 3d imaging through circularly symmetric pupil engineering,” Biomed. Opt. Express 9(2), 437–446 (2018).
[Crossref]

2017 (1)

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

2016 (3)

N. C. Pégard, H.-Y. Liu, N. Antipa, M. Gerlock, H. Adesnik, and L. Waller, “Compressive light-field microscopy for 3d neural activity recording,” Optica 3(5), 517–524 (2016).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

2015 (1)

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

2014 (5)

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

J. M. Jabbour, B. H. Malik, C. Olsovsky, R. Cuenca, S. Cheng, J. A. Jo, Y.-S. L. Cheng, J. M. Wright, and K. C. Maitland, “Optical axial scanning in confocal microscopy using an electrically tunable lens,” Biomed. Opt. Express 5(2), 645–652 (2014).
[Crossref]

N. Cohen, S. Yang, A. Andalman, M. Broxton, L. Grosenick, K. Deisseroth, M. Horowitz, and M. Levoy, “Enhancing the performance of the light field microscope using wavefront coding,” Opt. Express 22(20), 24817–24839 (2014).
[Crossref]

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

2013 (2)

2009 (1)

2008 (1)

2006 (1)

M. Levoy, R. Ng, A. Adams, M. Footer, and M. Horowitz, “Light field microscopy,” ACM Trans. Graph. 25(3), 924–934 (2006).
[Crossref]

2003 (1)

2001 (1)

1995 (1)

1960 (1)

Abrahamsson, S.

S. Abrahamsson, S. Usawa, and M. Gustafsson, “A new approach to extended focus for high-speed high-resolution biological microscopy,” in Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XIII, vol. 6090 (International Society for Optics and Photonics, 2006), p. 60900N.

Adams, A.

M. Levoy, R. Ng, A. Adams, M. Footer, and M. Horowitz, “Light field microscopy,” ACM Trans. Graph. 25(3), 924–934 (2006).
[Crossref]

Adesnik, H.

Andalman, A.

Antipa, N.

Bai, L.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Baragli, C.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Born, M.

M. Born and E. Wolf, “Asymptotic approximations to integrals,” in Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, (Elsevier, 2013), pp. 747–753.

Boyden, E. S.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Broxton, M.

Cai, B.

Cathey, W. T.

Chai, Y.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Cheng, S.

Cheng, Y.-S. L.

Chi, W.

Chu, K.

Cižmár, T.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Cohen, N.

Coll-Lladó, C.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Cong, L.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Cuenca, R.

Cui, M.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Dalgarno, H. I.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Deisseroth, K.

Dholakia, K.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Dowski, E. R.

Du, J.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Evans, G. J.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Ferrier, D. E.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Footer, M.

M. Levoy, R. Ng, A. Adams, M. Footer, and M. Horowitz, “Light field microscopy,” ACM Trans. Graph. 25(3), 924–934 (2006).
[Crossref]

George, N.

Gerlock, M.

Germain, R. N.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Goodman, J. W.

J. W. Goodman, “Wave-optics analysis of coherent optical systems,” in Introduction to Fourier Optics, (Roberts and Company Publishers, 2005), chap. 5.

Griffiths, V. A.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Grosenick, L.

Gunn-Moore, F. J.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Gustafsson, M.

S. Abrahamsson, S. Usawa, and M. Gustafsson, “A new approach to extended focus for high-speed high-resolution biological microscopy,” in Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XIII, vol. 6090 (International Society for Optics and Photonics, 2006), p. 60900N.

Hang, W.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Harris, G.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Harvey, A. R.

Hoffmann, M.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Horowitz, M.

Huo, J.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Jabbour, J. M.

Jackson, J.

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

Jo, J. A.

Kato, S.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Kawano, T.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Kirkby, P. A.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Koimtzis, T.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Kong, L.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Konstantinou, G.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Lämmermann, T.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Levoy, M.

Li, G.

Lin, C. P.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Little, J. P.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Liu, H.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Liu, H.-Y.

Lu, Y.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Maitland, K. C.

Malik, B. H.

Mertz, J.

Mezouari, S.

Nadella, K. N. S.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Ng, R.

M. Levoy, R. Ng, A. Adams, M. Footer, and M. Horowitz, “Light field microscopy,” ACM Trans. Graph. 25(3), 924–934 (2006).
[Crossref]

Nylk, J.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Olsovsky, C.

Pak, N.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Pégard, N. C.

Peterka, D. S.

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

S. Quirin, D. S. Peterka, and R. Yuste, “Instantaneous three-dimensional sensing using spatial light modulator illumination with extended depth of field imaging,” Opt. Express 21(13), 16007–16021 (2013).
[Crossref]

Po, M.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Prevedel, R.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Qin, Y.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Quirin, S.

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

S. Quirin, D. S. Peterka, and R. Yuste, “Instantaneous three-dimensional sensing using spatial light modulator illumination with extended depth of field imaging,” Opt. Express 21(13), 16007–16021 (2013).
[Crossref]

Raskar, R.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Roš, H.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Samuel, A. D.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Schafer, W. R.

W. R. Schafer, “Neurophysiological methods in c. elegans: an introduction,” in WormBook: The Online Review of C. elegans Biology [Internet], (WormBook, 2006).

Schrödel, T.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Shang, C.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Shao, S.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Shen, Y.

B. Cai, X. Zhai, Z. Wang, Y. Shen, R. Xu, Z. J. Smith, Q. Wen, and K. Chu, “Optical volumetric projection for fast 3d imaging through circularly symmetric pupil engineering,” Biomed. Opt. Express 9(2), 437–446 (2018).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Silver, R. A.

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

Smith, Z. J.

Tang, J.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Usawa, S.

S. Abrahamsson, S. Usawa, and M. Gustafsson, “A new approach to extended focus for high-speed high-resolution biological microscopy,” in Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XIII, vol. 6090 (International Society for Optics and Photonics, 2006), p. 60900N.

Vaziri, A.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Vettenburg, T.

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

Waller, L.

Wang, D.

Wang, K.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Wang, Z.

B. Cai, X. Zhai, Z. Wang, Y. Shen, R. Xu, Z. J. Smith, Q. Wen, and K. Chu, “Optical volumetric projection for fast 3d imaging through circularly symmetric pupil engineering,” Biomed. Opt. Express 9(2), 437–446 (2018).
[Crossref]

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Welford, W. T.

Wen, Q.

B. Cai, X. Zhai, Z. Wang, Y. Shen, R. Xu, Z. J. Smith, Q. Wen, and K. Chu, “Optical volumetric projection for fast 3d imaging through circularly symmetric pupil engineering,” Biomed. Opt. Express 9(2), 437–446 (2018).
[Crossref]

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Wetzstein, G.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Wolf, E.

M. Born and E. Wolf, “Asymptotic approximations to integrals,” in Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, (Elsevier, 2013), pp. 747–753.

Wright, J. M.

Wu, M.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Xu, R.

Xu, T.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Yang, S.

Yang, W.

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Ye, R.

Yoon, Y.-G.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Yu, Y.

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

Yuste, R.

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

S. Quirin, D. S. Peterka, and R. Yuste, “Instantaneous three-dimensional sensing using spatial light modulator illumination with extended depth of field imaging,” Opt. Express 21(13), 16007–16021 (2013).
[Crossref]

Zhai, X.

Zhang, H.

Zhang, Y.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Zhen, M.

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Zhong, C.

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Zhou, F.

Zimmer, M.

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

ACM Trans. Graph. (1)

M. Levoy, R. Ng, A. Adams, M. Footer, and M. Horowitz, “Light field microscopy,” ACM Trans. Graph. 25(3), 924–934 (2006).
[Crossref]

Appl. Opt. (2)

Biomed. Opt. Express (2)

eLife (2)

L. Cong, Z. Wang, Y. Chai, W. Hang, C. Shang, W. Yang, L. Bai, J. Du, K. Wang, and Q. Wen, “Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (danio rerio),” eLife 6, e28158 (2017).
[Crossref]

Y. Shen, Q. Wen, H. Liu, C. Zhong, Y. Qin, G. Harris, T. Kawano, M. Wu, T. Xu, A. D. Samuel, and Y. Zhang, “An extrasynaptic gabaergic signal modulates a pattern of forward movement in caenorhabditis elegans,” eLife 5, e14197 (2016).
[Crossref]

Front. Neural Circuits (1)

S. Quirin, J. Jackson, D. S. Peterka, and R. Yuste, “Simultaneous imaging of neural activity in three dimensions,” Front. Neural Circuits 8, 29 (2014).
[Crossref]

J. Opt. Soc. Am. (1)

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

Nat. Methods (4)

K. N. S. Nadella, H. Roš, C. Baragli, V. A. Griffiths, G. Konstantinou, T. Koimtzis, G. J. Evans, P. A. Kirkby, and R. A. Silver, “Random-access scanning microscopy for 3d imaging in awake behaving animals,” Nat. Methods 13(12), 1001–1004 (2016).
[Crossref]

L. Kong, J. Tang, J. P. Little, Y. Yu, T. Lämmermann, C. P. Lin, R. N. Germain, and M. Cui, “Continuous volumetric imaging via an optical phase-locked ultrasound lens,” Nat. Methods 12(8), 759–762 (2015).
[Crossref]

T. Vettenburg, H. I. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an airy beam,” Nat. Methods 11(5), 541–544 (2014).
[Crossref]

R. Prevedel, Y.-G. Yoon, M. Hoffmann, N. Pak, G. Wetzstein, S. Kato, T. Schrödel, R. Raskar, M. Zimmer, E. S. Boyden, and A. Vaziri, “Simultaneous whole-animal 3d imaging of neuronal activity using light-field microscopy,” Nat. Methods 11(7), 727–730 (2014).
[Crossref]

Opt. Express (3)

Opt. Lett. (2)

Optica (2)

Proc. Natl. Acad. Sci. (1)

T. Xu, J. Huo, S. Shao, M. Po, T. Kawano, Y. Lu, M. Wu, M. Zhen, and Q. Wen, “Descending pathway facilitates undulatory wave propagation in caenorhabditis elegans through gap junctions,” Proc. Natl. Acad. Sci. 115(19), E4493–E4502 (2018).
[Crossref]

Other (4)

W. R. Schafer, “Neurophysiological methods in c. elegans: an introduction,” in WormBook: The Online Review of C. elegans Biology [Internet], (WormBook, 2006).

S. Abrahamsson, S. Usawa, and M. Gustafsson, “A new approach to extended focus for high-speed high-resolution biological microscopy,” in Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XIII, vol. 6090 (International Society for Optics and Photonics, 2006), p. 60900N.

J. W. Goodman, “Wave-optics analysis of coherent optical systems,” in Introduction to Fourier Optics, (Roberts and Company Publishers, 2005), chap. 5.

M. Born and E. Wolf, “Asymptotic approximations to integrals,” in Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, (Elsevier, 2013), pp. 747–753.

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Figures (9)

Fig. 1.
Fig. 1. Schematic of the proposed imaging system. The back pupil plane II of the objective ( ${L_\textrm {1}}$ ) is relayed onto the spatial light modulator (plane III). The Fluorescent signals are recorded by a camera (plane IV) placed in the conjugate plane of the sample plane (plane I).
Fig. 2.
Fig. 2. Numerical study of different approximations of the defocus function for NA 0.3 objectives with defocus distance 65 $\mu \textrm {m}$ (a), NA 0.6 objectives with defocus distance 30 $\mu \textrm {m}$ (b) and NA 1.4 objectives with defocus distance 5 $\mu \textrm {m}$ (c). Theory-Nonparaxial and Theory-Paraxial indicates the difference between nonparaxial and paraxial approximation methods to theory, respectively.
Fig. 3.
Fig. 3. Phase profiles of the EDoF phase mask when NA=0.3 (a) and NA=0.6 (b). The difference between paraxial and nonparaxial approximation is more prominent when NA is larger. Accordingly PSFs with nonparaxial formula (c) will be more different than PSFs with paraxial formula (d).
Fig. 4.
Fig. 4. Curves of point spread function of the conventional system (a) and the proposed system (b). (c) Normalized central peak values vs axial distance.
Fig. 5.
Fig. 5. EDoF performance and its dependence on the objectives: XZ cross section of measured PSFs from the conventional system (a, c) and the EDoF system (b, d). (e, f) normalized central peak values vs axial distance. (a, b, e) are results measured with the same objective. (c, d, f) are with a different objective but with same magnification and NA.
Fig. 6.
Fig. 6. Imaging results of multi-layered beads. (a) Conventional imaging system. (b) Maximum-Intensity projections of the conventional axial scanning images. (c) The EDoF imaging system using cubic phase designs. (d) The EDoF imaging system using paraxial designs. (e) The EDoF imaging system using nonparaxial designs. (f) The percentage of fluorescent beads in different peak intensity ranges. Note that the images are stretched by contrast to show defocused beads. The arrows 1, 2 and 3 in (b) and (e) represent beads in the z plane of -20 $\mu m$ , 0 $\mu m$ , 10 $\mu m$ .
Fig. 7.
Fig. 7. Imaging results of brain tissue: typical raw images are captured with the conventional system (a) and the proposed system (b). (c) The Maximum-Intensity projection along the propagation axis with the conventional system. Arrows 1, 2 and 3 represent structures in the z plane of -20 $\mu m$ , 0 $\mu m$ , 10 $\mu m$ .
Fig. 8.
Fig. 8. Whole brain images of Caenorhabditis elegans. Snapshots acquired with (a) the conventional and (b) the proposed system. (c) is the Maximum-Intensity projection along z-axis of the conventional system. (d) The intensity distributions of the regions indicated by three lines in (a-c).
Fig. 9.
Fig. 9. Results using the fabricated phase mask. XZ cross section of measured PSFs (a) and normalized central peak values vs axial distance (b). (c) whole brain images of C.elegans.

Equations (19)

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

E 2 ( ρ 2 , z ) e j k ( ρ 2 2 + f 1 2 ρ 2 2 + ( f 1 + z ) 2 ) ,
W d t h e o r y ( ρ 2 , z ) = ρ 2 2  +  f 1 2 ρ 2 2  +  ( f 1 + z ) 2 .
W d N P ( ρ 2 , z ) = f 1 ρ 2 2 + f 1 2 z ,
W d P ( ρ 2 , z ) = 1 2 f 1 ( 1 f 1 + z f 1 ) ρ 2 2 = z 2 f 1 2 ρ 2 2 ,
E 3 ( ρ 3 , z ) e j [ k ( ( f 2 f 3 ρ 3 ) 2 + f 1 2 ( f 2 f 3 ρ 3 ) 2 + ( f 1 + z ) 2 ) + ϕ S L M ( ρ 3 ) ] ,
p s f ( ρ 4 , z ) | 0 ρ 3 max e j [ k ( ( f 2 f 3 ρ 3 ) 2 + f 1 2 ( f 2 f 3 ρ 3 ) 2 + ( f 1 + z ) 2 ) + ϕ S L M ( ρ 3 ) ] J 0 ( k ρ 3 ρ 4 f 4 ) ρ 3 d ρ 3 | 2 ,
p s f ( 0 , z ) | 0 ρ 3 max e j [ k ( ( f 2 f 3 ρ 3 ) 2 + f 1 2 ( f 2 f 3 ρ 3 ) 2 + ( f 1 + z ) 2 ) + ϕ S L M ( ρ 3 ) ] ρ 3 d ρ 3 | 2 .
p s f ( 0 , z ) ( ρ 3 ( 0 ) ( z ) ) 2 / | Φ ( ρ 3 ( 0 ) , z ) | ,
Φ ( ρ 3 , z ) = k f 1 ( f 2 f 3 ρ 3 ) 2 + f 1 2 z + ϕ S L M ( ρ 3 ) ,
Φ ( ρ 3 , z ) | ρ 3 = ρ 3 ( 0 ) = 0.
ϕ S L M ( ρ 3 ( 0 ) ) = k f 1 z ρ 3 ( 0 ) [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 3 2 ( f 2 f 3 ) 2 .
k f 1 ( f 2 f 3 ) 2 z f 0 2 2 ( f 2 f 3 ρ 3 ( 0 ) ) 2 [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 5 2 + ϕ S L M ( ρ 3 ( 0 ) ) = ( ρ 3 ( 0 ) ) 2 C .
ϕ S L M ( ρ 3 ( 0 ) ) ϕ S L M ( ρ 3 ( 0 ) ) [ f 0 2 2 ( f 2 f 3 ρ 3 ( 0 ) ) 2 ] ρ 3 ( 0 ) [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] = ( ρ 3 ( 0 ) ) 2 C .
ϕ S L M ( ρ 3 ( 0 ) ) = 1 20 C ( f 3 f 2 ) 4 [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 2 C 1 ( f 3 f 2 ) 2 [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 1 2 + C 2 .
ρ 3 ( 0 ) 5 C ( f 3 f 2 ) 2 [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] + C 1 ρ 3 ( 0 ) [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 3 2 = k f 1 z ρ 3 ( 0 ) [ ( f 2 f 3 ρ 3 ( 0 ) ) 2 + f 1 2 ] 3 2 ( f 2 f 3 ) 2 ,
C = f 3 4 5 k δ f 1 f 2 4 [ [ ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 [ 1 2 ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 ] ,
C 1 = k f 1 δ ( f 2 f 3 ) 2 [ 1 2 ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 [ ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 [ 1 2 ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 .
ϕ S L M ( ρ 3 ) = k f 1 δ [ 1 2 ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 [ ( f 2 f 3 ρ 3 ) 2 + f 1 2 ] 1 2 1 4 [ ( f 2 f 3 ρ 3 ) 2 + f 1 2 ] 2 [ ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 [ 1 2 ( f 2 f 3 ρ 3 max ) 2 + f 1 2 ] 5 2 + C 2 ,
ϕ S L M ( ρ 3 ) = k δ 2 f 2 2 f 1 2 ρ 3 2 f 3 2 ( 1 ρ 3 2 ( ρ 3 max ) 2 ) + C 2 ,

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