Abstract

Subsurface microscopy is often limited by poor image quality due to sample-induced aberrations. Adaptive optics (AO) can counter such aberrations, though generally over limited fields of view. In most applications, AO is either slow or requires a “guide star” in the sample to serve as a localized reference target. We describe a fast closed-loop feedback implementation of AO that requires no guide stars, where the sample itself serves as the reference. Several features of our implementation are new. First, it is based on a high-resolution, single-shot wavefront sensor that is compatible with extended samples. Second, it is applied to widefield (i.e., nonscanning) microscopy in a conjugate AO configuration that increases field of view. Third, it makes use of a fast algorithm to identify sample-induced aberrations using illumination from an arbitrarily shaped source. We present the principle of our technique and proof-of-concept experimental demonstrations.

© 2015 Optical Society of America

Full Article  |  PDF Article
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References

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2015 (3)

2014 (3)

M. J. Booth, “Adaptive optical microscopy: the ongoing quest for a perfect image,” Light 3, e165 (2014).
[Crossref]

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

2013 (3)

2012 (3)

2011 (2)

2010 (1)

2009 (3)

2008 (1)

2007 (2)

Z. Kam, P. Kner, D. Agard, and J. W. Sedat, “Modelling the application of adaptive optics to wide-field microscope live imaging,” J. Microsc. 226, 33–42 (2007).
[Crossref]

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32, 2309–2311 (2007).
[Crossref]

2006 (3)

M. Rueckel, J. A. Mack-Bucher, and W. Denk, “Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing,” Proc. Natl. Acad. Sci. USA 103, 17137–17142 (2006).
[Crossref]

T. E. Gureyev, Y. I. Nesterets, D. M. Paganin, A. Pogany, and S. W. Wilkins, “Linear algorithms for phase retrieval in the Fresnel region. 2. Partially coherent illumination,” Opt. Commun. 259, 569–580 (2006).
[Crossref]

S. Bernet, A. Jesacher, S. Fuerhapter, C. Maurer, and M. Ritsch-Marte, “Quantitative imaging of complex samples by spiral phase contrast microscopy,” Opt. Express 14, 3792–3805 (2006).
[Crossref]

2005 (1)

2004 (1)

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

2003 (2)

2002 (1)

M. J. Booth, M. A. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

2001 (2)

B. C. Platt and R. Shack, “History and principles of Shack-Hartmann wavefront sensing,” J. Refract. Surg. 17, S573–S577 (2001).

L. J. Allen and M. P. Oxley, “Phase retrieval from series of images obtained by defocus variation,” Opt. Commun. 199, 65–75 (2001).
[Crossref]

1998 (1)

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80, 2586–2589 (1998).
[Crossref]

1997 (1)

1992 (1)

1983 (1)

M. R. Teague, “Deterministic phase retrieval: a Green’s function solution,” J. Opt. Soc. Am. A 73, 1434–1441 (1983).
[Crossref]

Agard, D.

Z. Kam, P. Kner, D. Agard, and J. W. Sedat, “Modelling the application of adaptive optics to wide-field microscope live imaging,” J. Microsc. 226, 33–42 (2007).
[Crossref]

Allen, L. J.

L. J. Allen and M. P. Oxley, “Phase retrieval from series of images obtained by defocus variation,” Opt. Commun. 199, 65–75 (2001).
[Crossref]

Anastasio, M. A.

Arnison, M. R.

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

Azucena, O.

Barankov, R.

Barbastathis, G.

Beckers, J. M.

J. M. Beckers, “Increasing the size of the isoplanatic patch within multiconjugate adaptive optics,” in Proceedings of European Southern Observatory Conference and Workshop on Very Large Telescopes and Their Instrumentation (1988), pp. 693–703.

Bernet, S.

Betzig, E.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Bifano, T. G.

Bon, P.

Booth, M. J.

M. J. Booth, “Adaptive optical microscopy: the ongoing quest for a perfect image,” Light 3, e165 (2014).
[Crossref]

R. D. Simmonds and M. J. Booth, “Modelling of multi-conjugate adaptive optics for spatially variant aberrations in microscopy,” J. Opt. 15, 094010 (2013).
[Crossref]

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34, 2495–2497 (2009).
[Crossref]

M. J. Booth, M. A. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

Born, M.

M. Born and E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light (Cambridge University, 1999).

Botcherby, E. J.

Bronner, M. E.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Burns, D.

Carney, P. S.

Chen, D. C.

Chen, T.-W.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Chu, K. K.

Cogswell, C. J.

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

Crest, J.

Cui, M.

T.-W. Wu and M. Cui, “Numerical study of multi-conjugate large area wavefront correction for deep tissue microscopy,” Opt. Express 23, 7463–7470 (2015).
[Crossref]

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. USA 109, 8434–8439 (2012).
[Crossref]

Dainty, C.

Dauwels, J.

Débarre, D.

Denk, W.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, “Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing,” Proc. Natl. Acad. Sci. USA 103, 17137–17142 (2006).
[Crossref]

Ding, H.

Engerer, P.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Fienup, J. R.

Ford, T. N.

Fuerhapter, S.

Germain, R. N.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. USA 109, 8434–8439 (2012).
[Crossref]

Gillette, M. U.

Girkin, J. M.

Green, J. J.

Gureyev, T. E.

T. E. Gureyev, Y. I. Nesterets, D. M. Paganin, A. Pogany, and S. W. Wilkins, “Linear algorithms for phase retrieval in the Fresnel region. 2. Partially coherent illumination,” Opt. Commun. 259, 569–580 (2006).
[Crossref]

Iglesias, I.

Ishimaru, A.

A. Ishimaru, Wave Propagation and Scattering in Random Media (Wiley-IEEE, 1999).

Jesacher, A.

Ji, N.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Jingshan, Z.

Juškaitis, R.

M. J. Booth, M. A. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

Kam, Z.

Z. Kam, P. Kner, D. Agard, and J. W. Sedat, “Modelling the application of adaptive optics to wide-field microscope live imaging,” J. Microsc. 226, 33–42 (2007).
[Crossref]

Kerlin, A.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Kim, D. S.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Kner, P.

Z. Kam, P. Kner, D. Agard, and J. W. Sedat, “Modelling the application of adaptive optics to wide-field microscope live imaging,” J. Microsc. 226, 33–42 (2007).
[Crossref]

Knutsson, P.

Knutsson, P. A.

Kotadia, S.

Kubby, J.

Larkin, K. G.

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

Liang, J.

Liu, R.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Mack-Bucher, J. A.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, “Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing,” Proc. Natl. Acad. Sci. USA 103, 17137–17142 (2006).
[Crossref]

Marsh, P. N.

Maucort, G.

Maurer, C.

Mertz, J.

Milkie, D. E.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Miller, D. T.

Millet, L.

Mir, M.

Misgeld, T.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Monneret, S.

Morgan, R. M.

Mosk, A. P.

Mumm, J.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Neil, M. A. A.

M. J. Booth, M. A. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. USA 99, 5788–5792 (2002).
[Crossref]

Nesterets, Y. I.

T. E. Gureyev, Y. I. Nesterets, D. M. Paganin, A. Pogany, and S. W. Wilkins, “Linear algorithms for phase retrieval in the Fresnel region. 2. Partially coherent illumination,” Opt. Commun. 259, 569–580 (2006).
[Crossref]

Nugent, K.

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80, 2586–2589 (1998).
[Crossref]

Ohara, C. M.

Owner-Petersen, M.

Oxley, M. P.

L. J. Allen and M. P. Oxley, “Phase retrieval from series of images obtained by defocus variation,” Opt. Commun. 199, 65–75 (2001).
[Crossref]

Paganin, D.

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80, 2586–2589 (1998).
[Crossref]

Paganin, D. M.

T. E. Gureyev, Y. I. Nesterets, D. M. Paganin, A. Pogany, and S. W. Wilkins, “Linear algorithms for phase retrieval in the Fresnel region. 2. Partially coherent illumination,” Opt. Commun. 259, 569–580 (2006).
[Crossref]

Parthasarathy, A. B.

Paudel, H.

Paxman, R. G.

Petruccelli, J. C.

Platt, B. C.

B. C. Platt and R. Shack, “History and principles of Shack-Hartmann wavefront sensing,” J. Refract. Surg. 17, S573–S577 (2001).

Pogany, A.

T. E. Gureyev, Y. I. Nesterets, D. M. Paganin, A. Pogany, and S. W. Wilkins, “Linear algorithms for phase retrieval in the Fresnel region. 2. Partially coherent illumination,” Opt. Commun. 259, 569–580 (2006).
[Crossref]

Popescu, G.

Popovic, Z.

Poyneer, L. A.

Redding, D. C.

Ritsch-Marte, M.

Rogers, J.

Rueckel, M.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, “Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing,” Proc. Natl. Acad. Sci. USA 103, 17137–17142 (2006).
[Crossref]

Saxena, A.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
[Crossref]

Schoonover, R. W.

Schulz, T. J.

Sedat, J. W.

Z. Kam, P. Kner, D. Agard, and J. W. Sedat, “Modelling the application of adaptive optics to wide-field microscope live imaging,” J. Microsc. 226, 33–42 (2007).
[Crossref]

Shack, R.

B. C. Platt and R. Shack, “History and principles of Shack-Hartmann wavefront sensing,” J. Refract. Surg. 17, S573–S577 (2001).

Sheppard, C. J. R.

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

Sidick, E.

Simmonds, R. D.

R. D. Simmonds and M. J. Booth, “Modelling of multi-conjugate adaptive optics for spatially variant aberrations in microscopy,” J. Opt. 15, 094010 (2013).
[Crossref]

Smith, N. I.

M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, “Linear phase imaging using differential interference contrast microscopy,” J. Microsc. 214, 7–12 (2004).
[Crossref]

Srinivas, S.

Sullivan, W.

Sun, W.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Tan, Z.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11, 1037–1040 (2014).
[Crossref]

Tang, J.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. USA 109, 8434–8439 (2012).
[Crossref]

Tao, X.

Teague, M. R.

M. R. Teague, “Deterministic phase retrieval: a Green’s function solution,” J. Opt. Soc. Am. A 73, 1434–1441 (1983).
[Crossref]

Thaung, J.

Tian, L.

Tyson, R.

R. Tyson, Principles of Adaptive Optics, 3rd ed., Series in Optics and Optoelectronics (CRC Press, 2010).

Unarunotai, S.

Vellekoop, I. M.

Waller, L.

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Supplementary Material (1)

NameDescription
» Visualization 1: AVI (16010 KB)      System demonstration video showing real-time AO while sample and aberrations are sporadically translated.

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Figures (6)

Fig. 1.
Fig. 1.

Geometry of focal and aberration planes.

Fig. 2.
Fig. 2.

Experimental setup. A trans-illuminated sample followed by a phase screen is imaged onto a science camera (lenses f1–f5) with magnification 4.6 × (imaging path in red; vertical dashed lines denote intermediate image planes). A DM is inserted into the optical path conjugate to the phase screen, and imaged with a PAW sensor comprising a main lens (f6) and quatrefoil lens f7 (inset) in a 3f configuration (wavefront sensing path in green). A PAW field stop prevents overlap of the four oblique-detection images projected onto the PAW camera. The DM and PAW sensor are mounted on a translatable stage enabling adjustable conjugation. Lens focal lengths: f 1 = 50 mm , f 2 = 100 mm , f 3 = 100 mm , f 4 = 300 mm , f 5 = 250 mm , f 6 = 200 mm , and f 7 = 250 mm .

Fig. 3.
Fig. 3.

Aberrated images of a 1951 USAF target sample (a) without and (b) with AO correction; (c) and (d) corresponding highlighted zooms.

Fig. 4.
Fig. 4.

Images of mammal elastic cartilage with (a) no aberrations (no phase screen, DM flat); (b) uncorrected (phase screen, DM flat); and (c) corrected (phase screen, AO on). The optimized DM actuator pattern is shown in panel (d). Note the apparent periodic structure corresponding to the negative of the phase screen structure.

Fig. 5.
Fig. 5.

Aberrated images of mammal elastic cartilage (a) without and (b) with AO correction. See also Visualization 1 showing a video of (b) as the sample and aberrations are sporadically translated.

Fig. 6.
Fig. 6.

Convergence of AO correction as a function of feedback iteration. Normalized rms image error is shown for different feedback gains g .

Equations (6)

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F ( ρ ) = L ( ρ , s ^ ) s ^ d 2 s ^ ,
J z ( ρ c , ρ d ) = 1 z 2 I 0 ( ρ 0 ) e i 2 π λ ¯ z ( ρ c ρ 0 ) · ρ d cos θ cos θ d 2 ρ 0 ,
J z ( ρ c , ρ d ) = L z ( ρ c , s ^ ) e i 2 π λ ¯ ρ d · s ^ d 2 s ^ ,
ρ d J z ( ρ c , ρ d ) | ρ d = 0 = i 2 π λ ¯ F z ( ρ c ) .
I z ( ρ c ) = 1 z 2 I 0 ( ρ 0 ) χ ( | ρ c ρ 0 | z ) d 2 ρ 0 ,
Θ z ( ρ c ) = 1 z 3 I z ( ρ c ) ( ρ c ρ 0 ) I 0 ( ρ 0 ) χ ( | ρ c ρ 0 | z ) d 2 ρ 0 ,

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