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  • Review Article
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Deep optical imaging within complex scattering media

Nature Reviews Physics volume 2, pages 141–158 (2020)Cite this article

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Abstract

Optical imaging has had a central role in elucidating the underlying biological and physiological mechanisms in living specimens owing to its high spatial resolution, molecular specificity and minimal invasiveness. However, its working depth for in vivo imaging is extremely shallow, and thus reactions occurring deep inside living specimens remain out of reach. This problem originates primarily from multiple light scattering caused by the inhomogeneity of tissue obscuring the desired image information. Adaptive optical microscopy, which minimizes the effect of sample-induced aberrations, has to date been the most effective approach to addressing this problem, but its performance has plateaued because it can suppress only lower-order perturbations. To achieve an imaging depth beyond this conventional limit, there is increasing interest in exploiting the physics governing multiple light scattering. New approaches have emerged based on the deterministic measurement and/or control of multiple-scattered waves, rather than their stochastic and statistical treatment. In this Review, we provide an overview of recent developments in this area, with a focus on approaches that achieve a microscopic spatial resolution while remaining useful for in vivo imaging, and discuss their present limitations and future prospects.

Key points

  • Optical microscopy is an indispensable tool in biology and medicine owing to its high spatial resolution, molecular specificity and minimal invasiveness, but it is limited to the interrogation of superficial layers for in vivo imaging.

  • The intensity of single-scattered waves used in conventional imaging decreases exponentially with depth; thus, the imaging depth limits are set by the detector dynamic range and the efficiency of the gating operations.

  • Approaches that make deterministic use of the abundant multiple-scattered (MS) waves have been proposed to enable deep optical imaging while maintaining the microscopic spatial resolving power.

  • Recording and controlling the wavefront of MS waves enables a complex scattering layer to be converted into a focusing lens, leading to the development of an ultrathin endoscope.

  • Acousto-optic interactions and wavefront sensing and/or control are integrated to exploit the large penetration depth of ultrasound and high spatial resolution of optical imaging.

  • Reflection-matrix approaches that record and process all MS waves enable the correction of sample-induced aberrations, exploitation of multiple scattering signals and suppression of multiple scattering noise, allowing for imaging at depths greater than those accessible with conventional confocal and adaptive optics microscopy.

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Fig. 1: Effects of multiple light scattering on imaging depth.
Fig. 2: Point optimization by wavefront shaping and its imaging applications.
Fig. 3: TM approach to image transfer and its application in endomicroscopy.
Fig. 4: Non-invasive imaging using speckle correlations and memory effects.
Fig. 5: Ultrasound-mediated optical wavefront shaping and imaging.
Fig. 6: Scattering and aberration suppression using a time-gated reflection-matrix approach.
Fig. 7: Eigenchannels of a reflection matrix and their use in imaging.

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References

  1. Luker, G. D. & Luker, K. E. Optical imaging: current applications and future directions. J. Nucl. Med. 49, 1–4 (2008).

    Article  Google Scholar 

  2. Wilt, B. A. et al. Advances in light microscopy for neuroscience. Annu. Rev. Neurosci. 32, 435–506 (2009).

    Article  Google Scholar 

  3. Hadjipanayis, C. G., Jiang, H., Roberts, D. W. & Yang, L. Current and future clinical applications for optical imaging of cancer: from intraoperative surgical guidance to cancer screening. Semin. Oncol. 38, 109–118 (2011).

    Article  Google Scholar 

  4. Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006).

    Article  ADS  Google Scholar 

  5. Rust, M. J., Bates, M. & Zhuang, X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3, 793–796 (2006).

    Article  Google Scholar 

  6. Klar, T. A., Jakobs, S., Dyba, M., Egner, A. & Hell, S. W. Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl Acad. Sci. USA 97, 8206–8210 (2000).

    Article  ADS  Google Scholar 

  7. Hell, S. W. Far-Field Optical nanoscopy. Science 316, 1153–1158 (2007).

    Article  ADS  Google Scholar 

  8. Tyson, R. K. Principles of Adaptive Optics (CRC Press, 2015).

  9. Liu, F., Yoo, K. M. & Alfano, R. R. Transmitted photon intensity through biological tissues within various time windows. Opt. Lett. 19, 740–742 (1994).

    Article  ADS  Google Scholar 

  10. Kang, S. et al. Imaging deep within a scattering medium using collective accumulation of single-scattered waves. Nat. Photonics 9, 253–258 (2015). The first report of the measurement of a wide-field time-gated reflection matrix.

    Article  ADS  Google Scholar 

  11. Badon, A., Boccara, A. C., Lerosey, G., Fink, M. & Aubry, A. Multiple scattering limit in optical microscopy. Opt. Express 25, 28914–28934 (2017).

    Article  ADS  Google Scholar 

  12. Dunsby, C. & French, P. M. W. Techniques for depth-resolved imaging through turbid media including coherence-gated imaging. J. Phys. D. Appl. Phys. 36, R207–R227 (2003). An early study on the development of single-scattering gating methods for deep optical imaging.

    Article  ADS  Google Scholar 

  13. Minsky, M. Microscopy apparatus. US Patent 3013467 (1961).

  14. Huang, D. et al. Optical coherence tomography. Science. 254, 1178–1181 (1991).

    Article  ADS  Google Scholar 

  15. Bouma, B. E. & Tearney, G. J. (eds) Handbook of Optical Coherence Tomography (Marcel Dekker, 2002).

  16. Pawley, J. (ed.) Handbook of Biological Confocal Microscopy (Springer, 2010).

  17. Yao, G. & Wang, L. V. Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue. Appl. Opt. 39, 659–664 (2000).

    Article  ADS  Google Scholar 

  18. Wang, L. V. Ultrasound-mediated biophotonic imaging: a review of acousto-optical tomography and photo-acoustic tomography. Dis. Markers 19, 123–138 (2004).

    Article  Google Scholar 

  19. Izatt, J. A., Hee, M. R., Owen, G. M., Swanson, E. A. & Fujimoto, J. G. Optical coherence microscopy in scattering media. Opt. Lett. 19, 590–592 (1994).

    Article  ADS  Google Scholar 

  20. Beaurepaire, E., Boccara, A. C., Lebec, M., Blanchot, L. & Saint-Jalmes, H. Full-field optical coherence microscopy. Opt. Lett. 23, 244–246 (1998).

    Article  ADS  Google Scholar 

  21. Oh, W. Y. et al. Ultrahigh-resolution full-field optical coherence microscopy using InGaAs camera. Opt. Express 14, 726–735 (2006).

    Article  ADS  Google Scholar 

  22. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    Article  ADS  Google Scholar 

  23. Hell, S. W. et al. Three-photon excitation in fluorescence microscopy. J. Biomed. Opt. 1, 71–74 (1996).

    Article  ADS  Google Scholar 

  24. Zipfel, W. R. et al. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl Acad. Sci. USA 100, 7075–7080 (2003).

    Article  ADS  Google Scholar 

  25. Barad, Y., Eisenberg, H., Horowitz, M. & Silberberg, Y. Nonlinear scanning laser microscopy by third harmonic generation. Appl. Phys. Lett. 70, 922–924 (1997).

    Article  ADS  Google Scholar 

  26. Papagiakoumou, E. et al. Functional patterned multiphoton excitation deep inside scattering tissue. Nat. Photonics 7, 274–278 (2013).

    Article  ADS  Google Scholar 

  27. Rowlands, C. J. et al. Wide-field three-photon excitation in biological samples. Light. Sci. Appl. 6, e16255 (2016).

    Article  Google Scholar 

  28. Adrià, E.-M. et al. Wide-field multiphoton imaging through scattering media without correction. Sci. Adv. 4, eaau1338 (2018).

    Article  Google Scholar 

  29. Booth, M. J. Adaptive optical microscopy: the ongoing quest for a perfect image. Light. Sci. Appl. 3, e165 (2014).

    Article  ADS  Google Scholar 

  30. Jang, M., Ko, H., Lee, W. K., Lee, J.-S. & Choi, W. Coherent space-gated microscopy: a step towards deep-tissue phase imaging of biological cells. Preprint at arXiv https://arxiv.org/abs/1811.02755 (2018).

  31. Durduran, T. et al. Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation. Opt. Lett. 29, 1766–1768 (2004).

    Article  ADS  Google Scholar 

  32. Ntziachristos, V., Yodh, A. G., Schnall, M. & Chance, B. Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement. Proc. Natl Acad. Sci. USA 97, 2767–2772 (2000).

    Article  ADS  Google Scholar 

  33. Wang, L. V. & Hu, S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335, 1458–1462 (2012).

    Article  ADS  Google Scholar 

  34. Vellekoop, I. M. & Mosk, A. P. Focusing coherent light through opaque strongly scattering media. Opt. Lett. 32, 2309–2311 (2007). The first demonstration of optical-wave focusing through a scattering layer.

    Article  ADS  Google Scholar 

  35. Yaqoob, Z., Psaltis, D., Feld, M. S. & Yang, C. Optical phase conjugation for turbidity suppression in biological samples. Nat. Photonics 2, 110–115 (2008).

    Article  ADS  Google Scholar 

  36. Dorokhov, O. N. On the coexistence of localized and extended electronic states in the metallic phase. Solid. State Commun. 51, 381–384 (1984).

    Article  ADS  Google Scholar 

  37. Feng, S., Kane, C., Lee, P. A. & Stone, A. D. Correlations and fluctuations of coherent wave transmission through disordered media. Phys. Rev. Lett. 61, 834–837 (1988).

    Article  ADS  Google Scholar 

  38. Freund, I., Rosenbluh, M. & Feng, S. Memory effects in propagation of optical waves through disordered media. Phys. Rev. Lett. 61, 2328–2331 (1988).

    Article  ADS  Google Scholar 

  39. Beenakker, C. W. J. Random-matrix theory of quantum transport. Rev. Mod. Phys. 69, 731–808 (1997).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  41. Rotter, S. & Gigan, S. Light fields in complex media: mesoscopic scattering meets wave control. Rev. Mod. Phys. 89, 015005 (2017).

    Article  ADS  Google Scholar 

  42. Fink, M. Time reversal of ultrasonic fields. I. Basic principles. IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 39, 555–566 (1992).

    Article  Google Scholar 

  43. Derode, A., Roux, P. & Fink, M. Robust acoustic time reversal with high-order multiple scattering. Phys. Rev. Lett. 75, 4206–4209 (1995).

    Article  ADS  Google Scholar 

  44. Fink, M. Time reversed acoustics. Phys. Today 50, 34–40 (1997).

    Article  Google Scholar 

  45. Lerosey, G. et al. Time reversal of electromagnetic waves. Phys. Rev. Lett. 92, 193904 (2004).

    Article  ADS  Google Scholar 

  46. Lerosey, G., de Rosny, J., Tourin, A., Derode, A. & Fink, M. Time reversal of wideband microwaves. Appl. Phys. Lett. 88, 154101 (2006).

    Article  ADS  Google Scholar 

  47. Vellekoop, I. M. & Mosk, A. P. Universal optimal transmission of light through disordered materials. Phys. Rev. Lett. 101, 120601 (2008).

    Article  ADS  Google Scholar 

  48. Kim, M., Choi, W., Yoon, C., Kim, G. H. & Choi, W. Relation between transmission eigenchannels and single-channel optimizing modes in a disordered medium. Opt. Lett. 38, 2994–2996 (2013).

    Article  ADS  Google Scholar 

  49. Katz, O., Small, E. & Silberberg, Y. Looking around corners and through thin turbid layers in real time with scattered incoherent light. Nat. Photonics 6, 549–553 (2012).

    Article  ADS  Google Scholar 

  50. Judkewitz, B., Horstmeyer, R., Vellekoop, I. M., Papadopoulos, I. N. & Yang, C. Translation correlations in anisotropically scattering media. Nat. Phys. 11, 684–689 (2015).

    Article  Google Scholar 

  51. Vellekoop, I. M., Lagendijk, A. & Mosk, A. P. Exploiting disorder for perfect focusing. Nat. Photonics 4, 320–322 (2010).

    Article  Google Scholar 

  52. van Putten, E. G. et al. Scattering lens resolves sub-100 nm structures with visible light. Phys. Rev. Lett. 106, 193905 (2011).

    Article  ADS  Google Scholar 

  53. Park, J.-H. et al. Subwavelength light focusing using random nanoparticles. Nat. Photonics 7, 454–458 (2013).

    Article  ADS  Google Scholar 

  54. Choi, W. et al. Control of randomly scattered surface plasmon polaritons for multiple-input and multiple-output plasmonic switching devices. Nat. Commun. 8, 14636 (2017).

    Article  ADS  Google Scholar 

  55. Gjonaj, B. et al. Focusing and scanning microscopy with propagating surface plasmons. Phys. Rev. Lett. 110, 266804 (2013).

    Article  ADS  Google Scholar 

  56. Seo, E. et al. Far-field control of focusing plasmonic waves through disordered nanoholes. Opt. Lett. 39, 5838–5841 (2014).

    Article  ADS  Google Scholar 

  57. Vellekoop, I. M. Feedback-based wavefront shaping. Opt. Express 23, 12189–12206 (2015).

    Article  ADS  Google Scholar 

  58. Wang, D. et al. Focusing through dynamic tissue with millisecond digital optical phase conjugation. Optica 2, 728–735 (2015).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  60. Blochet, B., Bourdieu, L. & Gigan, S. Focusing light through dynamical samples using fast continuous wavefront optimization. Opt. Lett. 42, 4994–4997 (2017).

    Article  ADS  Google Scholar 

  61. Liu, Y., Ma, C., Shen, Y., Shi, J. & Wang, L. V. Focusing light inside dynamic scattering media with millisecond digital optical phase conjugation. Optica 4, 280–288 (2017).

    Article  ADS  Google Scholar 

  62. Feldkhun, D., Tzang, O., Wagner, K. H. & Piestun, R. Focusing and scanning through scattering media in microseconds. Optica 6, 72–75 (2019).

    Article  ADS  Google Scholar 

  63. Ji, N., Milkie, D. E. & Betzig, E. Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues. Nat. Methods 7, 141–147 (2009).

    Article  Google Scholar 

  64. Park, J.-H., Sun, W. & Cui, M. High-resolution in vivo imaging of mouse brain through the intact skull. Proc. Natl Acad. Sci. USA 112, 9236–9241 (2015).

    Article  ADS  Google Scholar 

  65. Frostig, H. et al. Focusing light by wavefront shaping through disorder and nonlinearity. Optica 4, 1073–1079 (2017).

    Article  ADS  Google Scholar 

  66. Ruan, H. et al. Focusing light inside scattering media with magnetic-particle-guided wavefront shaping. Optica 4, 1337–1343 (2017).

    Article  ADS  Google Scholar 

  67. Florentin, R. et al. Shaping the light amplified in a multimode fiber. Light Sci. Appl. 6, e16208 (2017).

    Article  Google Scholar 

  68. Shen, Y., Liu, Y., Ma, C. & Wang, L. V. Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 cm in thickness with digital optical phase conjugation. J. Biomed. Opt. 21, 085001 (2016).

    Article  ADS  Google Scholar 

  69. Popoff, S., Lerosey, G., Fink, M., Boccara, A. C. & Gigan, S. Image transmission through an opaque material. Nat. Commun. 1, 81 (2010).

    Article  ADS  Google Scholar 

  70. Popoff, S. M. et al. Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media. Phys. Rev. Lett. 104, 100601 (2010). The first report of the measurement of a transmission matrix in optics.

    Article  ADS  Google Scholar 

  71. Choi, Y. et al. Overcoming the diffraction limit using multiple light scattering in a highly disordered medium. Phys. Rev. Lett. 107, 023902 (2011).

    Article  ADS  Google Scholar 

  72. Choi, Y. et al. Synthetic aperture microscopy for high resolution imaging through a turbid medium. Opt. Lett. 36, 4263–4265 (2011).

    Article  ADS  Google Scholar 

  73. van Putten, E. & Mosk, A. The information age in optics: measuring the transmission matrix. Physics 3, 22 (2010).

    Article  Google Scholar 

  74. Choi, Y. et al. Scanner-free and wide-field endoscopic imaging by using a single multimode optical fiber. Phys. Rev. Lett. 109, 203901 (2012).

    Article  ADS  Google Scholar 

  75. Choi, Y., Yoon, C., Kim, M., Choi, W. & Choi, W. Optical imaging with the use of a scattering lens. IEEE J. Sel. Top. Quantum Electron. 20, 6800213 (2014).

    Google Scholar 

  76. Yoon, C. et al. Removal of back-reflection noise at ultrathin imaging probes by the single-core illumination and wide-field detection. Sci. Rep. 7, 6524 (2017).

    Article  ADS  Google Scholar 

  77. Bianchi, S. & Di Leonardo, R. A multi-mode fiber probe for holographic micromanipulation and microscopy. Lab. Chip 12, 635–639 (2012). The first report of imaging through a multimode fibre.

    Article  Google Scholar 

  78. Bianchi, S. et al. Focusing and imaging with increased numerical apertures through multimode fibers with micro-fabricated optics. Opt. Lett. 38, 4935–4938 (2013).

    Article  ADS  Google Scholar 

  79. Čižmár, T. & Dholakia, K. Exploiting multimode waveguides for pure fibre-based imaging. Nat. Commun. 3, 1027 (2012).

    Article  ADS  Google Scholar 

  80. Čižmár, T. & Dholakia, K. Shaping the light transmission through a multimode optical fibre: complex transformation analysis and applications in biophotonics. Opt. Express 19, 18871–18884 (2011).

    Article  ADS  Google Scholar 

  81. Kim, D. et al. Toward a miniature endomicroscope: pixelation-free and diffraction-limited imaging through a fiber bundle. Opt. Lett. 39, 1921–1924 (2014).

    Article  ADS  Google Scholar 

  82. Ohayon, S., Caravaca-Aguirre, A., Piestun, R. & DiCarlo, J. J. Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging. Biomed. Opt. Express 9, 1492–1509 (2018).

    Article  Google Scholar 

  83. Caravaca-Aguirre, A. M. & Piestun, R. Single multimode fiber endoscope. Opt. Express 25, 1656–1665 (2017).

    Article  ADS  Google Scholar 

  84. Turtaev, S. et al. High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging. Light. Sci. Appl. 7, 92 (2018).

    Article  ADS  Google Scholar 

  85. Loterie, D. et al. Digital confocal microscopy through a multimode fiber. Opt. Express 23, 23845–23858 (2015).

    Article  ADS  Google Scholar 

  86. Morales-Delgado, E. E., Psaltis, D. & Moser, C. Two-photon imaging through a multimode fiber. Opt. Express 23, 32158–32170 (2015).

    Article  ADS  Google Scholar 

  87. Drémeau, A. et al. 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).

    Article  ADS  Google Scholar 

  88. del Hougne, P., Rajaei, B., Daudet, L. & Lerosey, G. Intensity-only measurement of partially uncontrollable transmission matrix: demonstration with wave-field shaping in a microwave cavity. Opt. Express 24, 18631–18641 (2016).

    Article  ADS  Google Scholar 

  89. Porat, A. et al. Widefield lensless imaging through a fiber bundle via speckle correlations. Opt. Express 24, 16835–16855 (2016).

    Article  ADS  Google Scholar 

  90. Farahi, S., Ziegler, D., Papadopoulos, I. N., Psaltis, D. & Moser, C. Dynamic bending compensation while focusing through a multimode fiber. Opt. Express 21, 22504–22514 (2013).

    Article  ADS  Google Scholar 

  91. Loterie, D., Psaltis, D. & Moser, C. Bend translation in multimode fiber imaging. Opt. Express 25, 6263–6273 (2017).

    Article  ADS  Google Scholar 

  92. Plöschner, M., Tyc, T. & Čižmár, T. Seeing through chaos in multimode fibres. Nat. Photonics 9, 529–535 (2015).

    Article  ADS  Google Scholar 

  93. Boonzajer Flaes, D. E. et al. Robustness of light-transport processes to bending deformations in graded-index multimode waveguides. Phys. Rev. Lett. 120, 233901 (2018).

    Article  ADS  Google Scholar 

  94. Freund, I. Looking through walls and around corners. Phys. A 168, 49–65 (1990).

    Article  Google Scholar 

  95. Akkermans, E. & Montambaux, G. Mesoscopic Physics of Electrons and Photons (Cambridge Univ. Press, 2007).

  96. Osnabrugge, G., Horstmeyer, R., Papadopoulos, I. N., Judkewitz, B. & Vellekoop, I. M. The generalized optical memory effect. Optica 4, 886–892 (2017).

    Article  ADS  Google Scholar 

  97. Bertolotti, J. et al. Non-invasive imaging through opaque scattering layers. Nature 491, 232–234 (2012). The first study to use the optical memory effect for epi-fluorescence imaging.

    Article  ADS  Google Scholar 

  98. Katz, O., Heidmann, P., Fink, M. & Gigan, S. Non-invasive single-shot imaging through scattering layers and around corners via speckle correlations. Nat. Photonics 8, 784–790 (2014).

    Article  ADS  Google Scholar 

  99. Yang, X., Pu, Y. & Psaltis, D. Imaging blood cells through scattering biological tissue using speckle scanning microscopy. Opt. Express 22, 3405–3413 (2014).

    Article  ADS  Google Scholar 

  100. Schott, S., Bertolotti, J., Léger, J.-F., Bourdieu, L. & Gigan, S. Characterization of the angular memory effect of scattered light in biological tissues. Opt. Express 23, 13505–13516 (2015).

    Article  ADS  Google Scholar 

  101. Amitonova, L. V., Mosk, A. P. & Pinkse, P. W. H. Rotational memory effect of a multimode fiber. Opt. Express 23, 20569–20575 (2015).

    Article  ADS  Google Scholar 

  102. Stasio, N., Moser, C. & Psaltis, D. Calibration-free imaging through a multicore fiber using speckle scanning microscopy. Opt. Lett. 41, 3078–3081 (2016).

    Article  ADS  Google Scholar 

  103. Fienup, J. R. Phase retrieval algorithms: a comparison. Appl. Opt. 21, 2758–2769 (1982).

    Article  ADS  Google Scholar 

  104. Fienup, J. R. Reconstruction of an object from the modulus of its Fourier transform. Opt. Lett. 3, 27–29 (2008).

    Article  ADS  Google Scholar 

  105. Papadopoulos, I. N., Jouhanneau, J. S., Poulet, J. F. A. & Judkewitz, B. Scattering compensation by focus scanning holographic aberration probing (F-SHARP). Nat. Photonics 11, 116–123 (2017).

    Article  ADS  Google Scholar 

  106. Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

    Article  Google Scholar 

  107. Szabo, T. L. Diagnostic Ultrasound Imaging: Inside Out (Elsevier, 2004).

  108. Elson, D. S., Li, R., Dunsby, C., Eckersley, R. & Tang, M. X. Ultrasound-mediated optical tomography: a review of current methods. Interface Focus. 1, 632–648 (2011).

    Article  Google Scholar 

  109. Yao, G. & Wang, L. V. in Biomedical Optical Spectroscopy and Diagnostics (Optical Society of America, 2000).

  110. Wang, L. V. Prospects of photoacoustic tomography. Med. Phys. 35, 5758–5767 (2008).

    Article  Google Scholar 

  111. Wang, L. V. (ed.) Photoacoustic Imaging and Spectroscopy (CRC press, 2017).

  112. Culjat, M. O., Goldenberg, D., Tewari, P. & Singh, R. S. A review of tissue substitutes for ultrasound imaging. Ultrasound Med. Biol. 36, 861–873 (2010).

    Article  Google Scholar 

  113. Horstmeyer, R., Ruan, H. & Yang, C. Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue. Nat. Photonics 9, 563–571 (2015).

    Article  ADS  Google Scholar 

  114. Jang, M., Sentenac, A. & Yang, C. Optical phase conjugation (OPC)-assisted isotropic focusing. Opt. Express 21, 8781–8792 (2013).

    Article  ADS  Google Scholar 

  115. Xu, X., Liu, H. & Wang, L. V. Time-reversed ultrasonically encoded optical focusing into scattering media. Nat. Photonics 5, 154–157 (2011). The first study to combine acousto-optic modulation and optical phase conjugation for optical imaging in a scattering medium.

    Article  ADS  Google Scholar 

  116. Wang, Y. M., Judkewitz, B., Dimarzio, C. A. & Yang, C. Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light. Nat. Commun. 3, 928 (2012).

    Article  ADS  Google Scholar 

  117. Si, K., Fiolka, R. & Cui, M. Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation. Nat. Photonics 6, 657–661 (2012).

    Article  ADS  Google Scholar 

  118. Si, K., Fiolka, R. & Cui, M. Breaking the spatial resolution barrier via iterative sound-light interaction in deep tissue microscopy. Sci. Rep. 2, 748 (2012).

    Article  ADS  Google Scholar 

  119. Ruan, H., Jang, M., Judkewitz, B. & Yang, C. Iterative time-reversed ultrasonically encoded light focusing in backscattering mode. Sci. Rep. 4, 7156 (2014).

    Article  ADS  Google Scholar 

  120. Judkewitz, B., Wang, Y. M., Horstmeyer, R., Mathy, A. & Yang, C. Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE). Nat. Photonics 7, 300–305 (2013).

    Article  ADS  Google Scholar 

  121. Katz, O., Ramaz, F., Gigan, S. & Fink, M. Controlling light in complex media beyond the acoustic diffraction-limit using the acousto-optic transmission matrix. Nat. Commun. 10, 717 (2019).

    Article  ADS  Google Scholar 

  122. Izatt, J. A., Swanson, E. A., Fujimoto, J. G., Hee, M. R. & Owen, G. M. Optical coherence microscopy in scattering media. Opt. Lett. 19, 590–592 (2008).

    Article  ADS  Google Scholar 

  123. Chaigne, T. et al. Controlling light in scattering media non-invasively using the photoacoustic transmission matrix. Nat. Photonics 8, 58–64 (2014).

    Article  ADS  Google Scholar 

  124. Lai, P., Wang, L., Tay, J. W. & Wang, L. V. Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media. Nat. Photonics 9, 126–132 (2015).

    Article  ADS  Google Scholar 

  125. Conkey, D. B. et al. Super-resolution photoacoustic imaging through a scattering wall. Nat. Commun. 6, 7902 (2015).

    Article  ADS  Google Scholar 

  126. Kang, S. et al. High-resolution adaptive optical imaging within thick scattering media using closed-loop accumulation of single scattering. Nat. Commun. 8, 2157 (2017). A report of a reflection matrix analysis algorithm to correct aberrations without using guide stars.

    Article  ADS  Google Scholar 

  127. Kim, M. et al. Label-free neuroimaging in vivo using synchronous angular scanning microscopy with single-scattering accumulation algorithm. Nat. Commun. 10, 3152 (2019).

    Article  ADS  Google Scholar 

  128. Colomb, T. et al. Numerical parametric lens for shifting, magnification, and complete aberration compensation in digital holographic microscopy. J. Opt. Soc. Am. A 23, 3177–3190 (2006).

    Article  ADS  Google Scholar 

  129. Boppart, S. A. et al. Computational adaptive optics for broadband optical interferometric tomography of biological tissue. Proc. Natl Acad. Sci. USA 109, 933505 (2012).

    Google Scholar 

  130. Shemonski, N. D. et al. Computational high-resolution optical imaging of the living human retina. Nat. Photonics 9, 440–443 (2015).

    Article  ADS  Google Scholar 

  131. Zheng, G., Ou, X., Horstmeyer, R. & Yang, C. Characterization of spatially varying aberrations for wide field-of-view microscopy. Opt. Express 21, 15131–15143 (2013).

    Article  ADS  Google Scholar 

  132. Pozzi, P. et al. Anisoplanatic adaptive optics in parallelized laser scanning microscopy. Preprint at arXiv https://arxiv.org/abs/1809.07529 (2018).

  133. Kim, M. et al. Maximal energy transport through disordered media with the implementation of transmission eigenchannels. Nat. Photonics 6, 581–585 (2012).

    Article  ADS  Google Scholar 

  134. Prada, C. & Fink, M. Eigenmodes of the time reversal operator: a solution to selective focusing in multiple-target media. Wave Motion 20, 151–163 (1994).

    Article  MathSciNet  MATH  Google Scholar 

  135. Aubry, A. & Derode, A. Random matrix theory applied to acoustic backscattering and imaging in complex media. Phys. Rev. Lett. 102, 084301 (2009).

    Article  ADS  Google Scholar 

  136. Popoff, S. M. et al. Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis. Phys. Rev. Lett. 107, 263901 (2011).

    Article  ADS  Google Scholar 

  137. Choi, Y. et al. Measurement of the time-resolved reflection matrix for enhancing light energy delivery into a scattering medium. Phys. Rev. Lett. 111, 243901 (2013).

    Article  ADS  Google Scholar 

  138. Jeong, S. et al. Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering. Nat. Photonics 12, 277–283 (2018).

    Article  ADS  Google Scholar 

  139. Badon, A. et al. Smart optical coherence tomography for ultra-deep imaging through highly scattering media. Sci. Adv. 2, e1600370 (2016). A study analysing the time-gated reflection eigenchannels for deep optical imaging.

    Article  ADS  Google Scholar 

  140. Kadobianskyi, M., Papadopoulos, I. N., Chaigne, T., Horstmeyer, R. & Judkewitz, B. Scattering correlations of time-gated light. Optica 5, 389–394 (2018).

    Article  ADS  Google Scholar 

  141. Osnabrugge, G., Amitonova, L. V. & Vellekoop, I. M. Blind focusing through strongly scattering media using wavefront shaping with nonlinear feedback. Opt. Express 27, 11673–11688 (2019).

    Article  ADS  Google Scholar 

  142. McCann, M. T., Jin, K. H. & Unser, M. Convolutional neural networks for inverse problems in imaging: a review. IEEE Signal. Process. Mag. 34, 85–95 (2017).

    Article  ADS  Google Scholar 

  143. Belthangady, C. & Royer, L. A. Applications, promises, and pitfalls of deep learning for fluorescence image reconstruction. Nat. Methods 16, 1215–1225 (2019).

    Article  Google Scholar 

  144. Barbastathis, G., Ozcan, A. & Situ, G. On the use of deep learning for computational imaging. Optica 6, 921–943 (2019).

    Article  ADS  Google Scholar 

  145. Turpin, A., Vishniakou, I. & Seelig, J.d. Light scattering control in transmission and reflection with neural networks. Opt. Express 26, 30911–30929 (2018).

    Article  ADS  Google Scholar 

  146. Rahmani, B., Loterie, D., Konstantinou, G., Psaltis, D. & Moser, C. Multimode optical fiber transmission with a deep learning network. Light. Sci. Appl. 7, 69 (2018).

    Article  ADS  Google Scholar 

  147. Kamilov, U. S. et al. Learning approach to optical tomography. Optica 2, 517–522 (2015).

    Article  ADS  Google Scholar 

  148. Sun, Y., Xia, Z. & Kamilov, U. S. Efficient and accurate inversion of multiple scattering with deep learning. Opt. Express 26, 14678–14688 (2018).

    Article  ADS  Google Scholar 

  149. Ntziachristos, V. Going deeper than microscopy: the optical imaging. Nat. Methods 7, 603–614 (2010).

    Article  Google Scholar 

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Acknowledgements

This research was supported by the Institute for Basic Science (grant no. IBS-R023-D1), the National Research Foundation of Korea (grant nos. NRF-2019R1C1C1008175 and NRF-2016R1A6A3A11936389), and the Catholic Medical Center Research Foundation in the programme year of 2018.

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Authors and Affiliations

  1. Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science, Seoul, Korea

    Seokchan Yoon, Mooseok Jang, Wonjun Choi & Wonshik Choi

  2. Department of Physics, Korea University, Seoul, Korea

    Seokchan Yoon, Mooseok Jang, Wonjun Choi & Wonshik Choi

  3. Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Moonseok Kim

  4. Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Moonseok Kim

  5. Department of Bio and Brain Engineering, KAIST, Daejeon, Korea

    Mooseok Jang

  6. School of Biomedical Engineering, Korea University, Seoul, Korea

    Youngwoon Choi

  7. Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA

    Sungsam Kang

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Glossary

Isoplanatic patch

The area over which the wavefront error remains almost the same.

Guide stars

Bright, point-like light sources or scatterers that provide a wavefront reference for measuring and correcting wavefront distortions in adaptive optics systems.

Point optimization

A method or algorithm that optimizes the point spread function by minimizing wavefront errors in adaptive optics systems.

Spatial light modulator

A device that modulates the amplitude, phase or polarization of light waves in space.

Optical memory effect

The phenomenon that speckle patterns of scattered light through thin and diffusive media are invariant to small tilts or shifts in an incident wavefront of light.

Digital micromirror devices

Micromirrors used for high-speed, efficient and reliable spatial-light modulation; originally invented to create video displays in digital projectors.

Epi-detection geometry

An imaging configuration in which an objective is used for both illumination and detection.

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Yoon, S., Kim, M., Jang, M. et al. Deep optical imaging within complex scattering media. Nat Rev Phys 2, 141–158 (2020). https://doi.org/10.1038/s42254-019-0143-2

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