Abstract

Light scattering inhibits high-resolution optical imaging, manipulation, and therapy deep inside biological tissue by preventing focusing. To form deep foci, wavefront-shaping techniques that break the optical diffusion limit have been developed. For in vivo applications, such focusing must provide a high gain, high speed, and a high focal peak-to-background ratio. However, none of the previous techniques meet these requirements simultaneously. Here, we overcome this challenge by rapidly measuring the perturbed optical field within a single camera exposure followed by adaptively time-reversing the phase-binarized perturbation. Consequently, a phase-conjugated wavefront is synthesized within a millisecond, two orders of magnitude shorter than the digitally achieved record. We demonstrate real-time focusing in dynamic scattering media and extend laser speckle contrast imaging to new depths. The unprecedented combination of a fast response, high gain, and high focusing contrast makes this work a major stride toward in vivo deep-tissue optical imaging, manipulation, and therapy.

© 2015 Optical Society of America

Full Article  |  PDF Article
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References

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2015 (6)

P. Lai, L. Wang, J. W. Tay, and L. V. Wang, “Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media,” Nat. Photonics 9, 126–132 (2015).
[Crossref]

Y. Liu, P. Lai, C. Ma, X. Xu, A. A. Grabar, and L. V. Wang, “Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light,” Nat. Commun. 6, 5904 (2015).
[Crossref]

M. Jang, H. Ruan, I. M. Vellekoop, B. Judkewitz, E. Chung, and C. Yang, “Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin,” Biomed. Opt. Express 6, 72–85 (2015).
[Crossref]

A. Drémeau, A. Liutkus, D. Martina, O. Katz, C. Schülke, F. Krzakala, S. Gigan, and L. Daudet, “Reference-less measurement of the transmission matrix of a highly scattering material using a DMD and phase retrieval techniques,” Opt. Express 23, 11898–11911 (2015).
[Crossref]

C. Ma, X. Xu, and L. V. Wang, “Analog time-reversed ultrasonically encoded light focusing inside scattering media with a 33,000× optical power gain,” Sci. Rep. 5, 8896 (2015).
[Crossref]

D. Wang, E. H. Zhou, J. Brake, H. Ruan, M. Jang, and C. Yang, “Focusing through dynamic tissue with millisecond digital optical phase conjugation,” Optica 2, 728–735 (2015).
[Crossref]

2014 (9)

J. W. Tay, J. Liang, and L. V. Wang, “Amplitude-masked photoacoustic wavefront shaping and application in flowmetry,” Opt. Lett. 39, 5499–5502 (2014).
[Crossref]

D. Kim, W. Choi, M. Kim, J. Moon, K. Seo, S. Ju, and W. Choi, “Implementing transmission eigenchannels of disordered media by a binary-control digital micromirror device,” Opt. Commun. 330, 35–39 (2014).
[Crossref]

D. Kim, J. Moon, M. Kim, T. D. Yang, J. Kim, E. Chung, and W. Choi, “Toward a miniature endomicroscope: pixelation-free and diffraction-limited imaging through a fiber bundle,” Opt. Lett. 39, 1921–1924 (2014).
[Crossref]

X. Zhang and P. Kner, “Binary wavefront optimization using a genetic algorithm,” J. Opt. 16, 125704 (2014).
[Crossref]

E. H. Zhou, H. Ruan, C. Yang, and B. Judkewitz, “Focusing on moving targets through scattering samples,” Optica 1, 227–232 (2014).
[Crossref]

S. N. Chandrasekaran, H. Ligtenberg, W. Steenbergen, and I. M. Vellekoop, “Using digital micromirror devices for focusing light through turbid media,” Proc. SPIE 8979, 897905 (2014).
[Crossref]

C. Ma, X. Xu, Y. Liu, and L. V. Wang, “Time-reversed adapted-perturbation (TRAP) optical focusing onto dynamic objects inside scattering media,” Nat. Photonics 8, 931–936 (2014).
[Crossref]

T. Chaigne, O. Katz, A. C. Boccara, M. Fink, E. Bossy, and S. Gigan, “Controlling light in scattering media non-invasively using the photoacoustic transmission matrix,” Nat. Photonics 8, 58–64 (2014).
[Crossref]

J. W. Tay, P. Lai, Y. Suzuki, and L. V. Wang, “Ultrasonically encoded wavefront shaping for focusing into random media,” Sci. Rep. 4, 3918 (2014).
[Crossref]

2013 (4)

A. M. Caravaca-Aguirre, E. Niv, D. B. Conkey, and R. Piestun, “Real-time resilient focusing through a bending multimode fiber,” Opt. Express 21, 12881–12887 (2013).
[Crossref]

L. Wang, J. Xia, J. Yao, K. I. Maslov, and L. V. Wang, “Ultrasonically encoded photoacoustic flowgraphy in biological tissue,” Phys. Rev. Lett. 111, 204301 (2013).
[Crossref]

B. Jayet, J.-P. Huignard, and F. Ramaz, “Optical phase conjugation in Nd: YVO4 for acousto-optic detection in scattering media,” Opt. Lett. 38, 1256–1258 (2013).
[Crossref]

A. M. Packer, B. Roska, and M. Häusser, “Targeting neurons and photons for optogenetics,” Nat. Neurosci. 16, 805–815 (2013).
[Crossref]

2012 (8)

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335, 1458–1462 (2012).
[Crossref]

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. USA 109, 22–27 (2012).
[Crossref]

D. B. Conkey, A. M. Caravaca-Aguirre, and R. Piestun, “High-speed scattering medium characterization with application to focusing light through turbid media,” Opt. Express 20, 1733–1740 (2012).
[Crossref]

A. P. Mosk, A. Lagendijk, G. Lerosey, and M. Fink, “Controlling waves in space and time for imaging and focusing in complex media,” Nat. Photonics 6, 283–292 (2012).
[Crossref]

I. M. Vellekoop, M. Cui, and C. Yang, “Digital optical phase conjugation of fluorescence in turbid tissue,” Appl. Phys. Lett. 101, 081108 (2012).
[Crossref]

K. Si, R. Fiolka, and M. Cui, “Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation,” Nat. Photonics 6, 657–661 (2012).
[Crossref]

Y. M. Wang, B. Judkewitz, C. A. DiMarzio, and C. Yang, “Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light,” Nat. Commun. 3, 928 (2012).
[Crossref]

Y. Liu, C. Zhang, and L. V. Wang, “Effects of light scattering on optical-resolution photoacoustic microscopy,” J. Biomed. Opt. 17, 126014 (2012).
[Crossref]

2011 (2)

X. Xu, H. Liu, and L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5, 154–157 (2011).
[Crossref]

D. Akbulut, T. J. Huisman, E. G. van Putten, W. L. Vos, and A. P. Mosk, “Focusing light through random photonic media by binary amplitude modulation,” Opt. Express 19, 4017–4029 (2011).
[Crossref]

2010 (6)

2009 (1)

M. Gross, M. Lesaffre, F. Ramaz, P. Delaye, G. Roosen, and A. C. Boccara, “Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography,” Eur. Phys. J. E 28, 173–182 (2009).
[Crossref]

2008 (2)

Z. Yaqoob, D. Psaltis, M. S. Feld, and C. Yang, “Optical phase conjugation for turbidity suppression in biological samples,” Nat. Photonics 2, 110–115 (2008).
[Crossref]

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature 452, 580–589 (2008).
[Crossref]

2007 (2)

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

C.-C. Wang, C. Thorpe, S. Thrun, M. Hebert, and H. Durrant-Whyte, “Simultaneous localization, mapping and moving object tracking,” Int. J. Rob. Res. 26, 889–916 (2007).
[Crossref]

2006 (1)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24, 848–851 (2006).
[Crossref]

2005 (1)

E. S. Boyden, F. Zhang, E. Bamberg, G. Nagel, and K. Deisseroth, “Millisecond-timescale, genetically targeted optical control of neural activity,” Nat. Neurosci. 8, 1263–1268 (2005).
[Crossref]

2004 (1)

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin, and A. Ben-Yakar, “Neurosurgery: functional regeneration after laser axotomy,” Nature 432, 822 (2004).
[Crossref]

2003 (1)

D. G. Grier, “A revolution in optical manipulation,” Nature 424, 810–816 (2003).
[Crossref]

1998 (1)

T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, and Q. Peng, “Photodynamic therapy,” J. Natl. Cancer Inst. 90, 889–905 (1998).

1997 (1)

1995 (1)

C. C. Dierickx, J. M. Casparian, V. Venugopalan, W. A. Farinelli, and R. R. Anderson, “Thermal relaxation of port-wine stain vessels probed in vivo: the need for 1–10-millisecond laser pulse treatment,” J. Invest. Dermatol. 105, 709–714 (1995).
[Crossref]

1989 (1)

D. Z. Anderson and J. Feinberg, “Optical novelty filters,” IEEE J. Quantum Electron. 25, 635–647 (1989).
[Crossref]

1988 (1)

R. Cudney, R. Pierce, and J. Feinberg, “The transient detection microscope,” Nature 332, 424–426 (1988).
[Crossref]

Aegerter, C. M.

Akbulut, D.

Anderson, D. Z.

D. Z. Anderson and J. Feinberg, “Optical novelty filters,” IEEE J. Quantum Electron. 25, 635–647 (1989).
[Crossref]

Anderson, R. R.

C. C. Dierickx, J. M. Casparian, V. Venugopalan, W. A. Farinelli, and R. R. Anderson, “Thermal relaxation of port-wine stain vessels probed in vivo: the need for 1–10-millisecond laser pulse treatment,” J. Invest. Dermatol. 105, 709–714 (1995).
[Crossref]

Angelsen, B.

L. Hatle and B. Angelsen, Doppler Ultrasound in Cardiology: Physical Principles and Clinical Applications (Lea & Febiger, 1985).

Bamberg, E.

E. S. Boyden, F. Zhang, E. Bamberg, G. Nagel, and K. Deisseroth, “Millisecond-timescale, genetically targeted optical control of neural activity,” Nat. Neurosci. 8, 1263–1268 (2005).
[Crossref]

Ben-Yakar, A.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin, and A. Ben-Yakar, “Neurosurgery: functional regeneration after laser axotomy,” Nature 432, 822 (2004).
[Crossref]

Betzig, E.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. USA 109, 22–27 (2012).
[Crossref]

Boas, D. A.

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

Boccara, A. C.

T. Chaigne, O. Katz, A. C. Boccara, M. Fink, E. Bossy, and S. Gigan, “Controlling light in scattering media non-invasively using the photoacoustic transmission matrix,” Nat. Photonics 8, 58–64 (2014).
[Crossref]

M. Gross, M. Lesaffre, F. Ramaz, P. Delaye, G. Roosen, and A. C. Boccara, “Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography,” Eur. Phys. J. E 28, 173–182 (2009).
[Crossref]

Bossy, E.

T. Chaigne, O. Katz, A. C. Boccara, M. Fink, E. Bossy, and S. Gigan, “Controlling light in scattering media non-invasively using the photoacoustic transmission matrix,” Nat. Photonics 8, 58–64 (2014).
[Crossref]

Boyden, E. S.

E. S. Boyden, F. Zhang, E. Bamberg, G. Nagel, and K. Deisseroth, “Millisecond-timescale, genetically targeted optical control of neural activity,” Nat. Neurosci. 8, 1263–1268 (2005).
[Crossref]

Brake, J.

Caravaca-Aguirre, A. M.

Casparian, J. M.

C. C. Dierickx, J. M. Casparian, V. Venugopalan, W. A. Farinelli, and R. R. Anderson, “Thermal relaxation of port-wine stain vessels probed in vivo: the need for 1–10-millisecond laser pulse treatment,” J. Invest. Dermatol. 105, 709–714 (1995).
[Crossref]

Chaigne, T.

T. Chaigne, O. Katz, A. C. Boccara, M. Fink, E. Bossy, and S. Gigan, “Controlling light in scattering media non-invasively using the photoacoustic transmission matrix,” Nat. Photonics 8, 58–64 (2014).
[Crossref]

Chandrasekaran, S. N.

S. N. Chandrasekaran, H. Ligtenberg, W. Steenbergen, and I. M. Vellekoop, “Using digital micromirror devices for focusing light through turbid media,” Proc. SPIE 8979, 897905 (2014).
[Crossref]

Chisholm, A. D.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin, and A. Ben-Yakar, “Neurosurgery: functional regeneration after laser axotomy,” Nature 432, 822 (2004).
[Crossref]

Choi, W.

D. Kim, W. Choi, M. Kim, J. Moon, K. Seo, S. Ju, and W. Choi, “Implementing transmission eigenchannels of disordered media by a binary-control digital micromirror device,” Opt. Commun. 330, 35–39 (2014).
[Crossref]

D. Kim, W. Choi, M. Kim, J. Moon, K. Seo, S. Ju, and W. Choi, “Implementing transmission eigenchannels of disordered media by a binary-control digital micromirror device,” Opt. Commun. 330, 35–39 (2014).
[Crossref]

D. Kim, J. Moon, M. Kim, T. D. Yang, J. Kim, E. Chung, and W. Choi, “Toward a miniature endomicroscope: pixelation-free and diffraction-limited imaging through a fiber bundle,” Opt. Lett. 39, 1921–1924 (2014).
[Crossref]

Chung, E.

Cinar, H.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin, and A. Ben-Yakar, “Neurosurgery: functional regeneration after laser axotomy,” Nature 432, 822 (2004).
[Crossref]

Cinar, H. N.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. Jin, and A. Ben-Yakar, “Neurosurgery: functional regeneration after laser axotomy,” Nature 432, 822 (2004).
[Crossref]

Conkey, D. B.

Cudney, R.

R. Cudney, R. Pierce, and J. Feinberg, “The transient detection microscope,” Nature 332, 424–426 (1988).
[Crossref]

Cui, M.

I. M. Vellekoop, M. Cui, and C. Yang, “Digital optical phase conjugation of fluorescence in turbid tissue,” Appl. Phys. Lett. 101, 081108 (2012).
[Crossref]

K. Si, R. Fiolka, and M. Cui, “Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation,” Nat. Photonics 6, 657–661 (2012).
[Crossref]

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Supplementary Material (1)

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Figures (6)

Fig. 1.
Fig. 1. Principle and schematic of b-TRAP focusing. (a)–(c) Principle of b-TRAP focusing (for details see text). (d) Schematic of the focusing method. The green (solid) arrows represent the light path in the probing process; the blue (slim) arrows show the light path in the time-reversal process. AOM, acousto-optic modulator; BS, beam splitter; CL, camera lens; L, lens; M, mirror; OS, optical shutter; sCMOS, scientific complementary metal oxide semiconductor camera; SF, spatial filter (zero-order block); SLM, spatial light modulator.
Fig. 2.
Fig. 2. Influence of field sampling scheme on the focusing quality under both target and medium decorrelations. (a)–(c) Time-dependent correlation coefficients of the scattered electromagnetic fields due to the target and the background (upper rows), and the field sampling schemes (lower rows). (a) Full-field (amplitude and phase) sampling using a phase-shifting scheme. (b) Amplitude-only sampling with double camera exposures and digital subtraction. (c) Amplitude-only sampling with single camera exposure and automatic analog subtraction. (d)–(f) Simulated focal light intensity distributions corresponding to the sampling schemes in (a)–(c), normalized by the peak intensity in (f).
Fig. 3.
Fig. 3. Influence of beam ratio IS/IR on the PBR of b-TRAP focusing. Discrete points are from numerical simulations, whereas lines are from the analytical model. The total number of controls is 100.
Fig. 4.
Fig. 4. Tracking a moving target inside scattering media. (a) Experimental scheme. The hair target between two scattering media moves back and forth on a motorized stage. (b) Measured time trace of the focal light intensity distribution. Each row depicts the light intensity distribution (integrated along y) at a fixed time point. Each column shows the temporal evolution of the intensity at a fixed position. Process repetition rate, 7 Hz. Inset: intensity profile along the dashed line.
Fig. 5.
Fig. 5. Tissue-mimicking phantom experiment. (a) Experimental arrangement. RBC, red blood cell; BS, beam splitter. (b) Focal light intensity distribution, each averaged over 100 speckle realizations, measured at different movement speeds of the media. (c) Medium’s correlation time as a function of its movement speed. The open triangles are measured data, whereas the solid line is the fitted curve. (d) Evolution of the focal intensity profile with increasing media decorrelation rate. Indices (i) through (iv) in (b)–(d) show different media’s correlation times as shown in (c). Scale bar, 500 μm.
Fig. 6.
Fig. 6. Deep-flow measurement with single-exposure b-TRAP focusing. (a) Simplified schematic. d, displacement; D, size of the moving particle. (b, c) Intensity maps of the exterior differential field (upper row, simulation) and interior focal field (lower row, experimental) at various target displacements. (d) Correlation of the scattered fields at different target displacements. Filled stars, simulation; dashed curve, theory. (e) Flow measurement results showing focal PBR as a function of flow speed, obtained at 500 and 800 Hz laser repetition rates. Discrete points are experimental data, whereas curves are theoretical fittings. Scale bar, 500 μm.

Equations (6)

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I(t1)=|ES(t1)|2+|ER|2+ES*(t1)ER+ES(t1)ER*.
I(t2)=|ES(t2)|2+|ER|2+ES*(t2)ER+ES(t2)ER*.
ΔI=I(t2)I(t1)=Δ|ES|2+ΔES*ER+ΔESER*,
I=|ES|2+2|ER|2ΔES*ERΔESER*,
tC[s]=1.2[μm]×{v[μm/s]}1,
PTRAP=Pmax{1{ξsinξ}/π},

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