Optoacoustic mesoscopy for biomedicine


Fuelled by innovation, optical microscopy plays a critical role in the life sciences and medicine, from basic discovery to clinical diagnostics. However, optical microscopy is limited by typical penetration depths of a few hundred micrometres for in vivo interrogations in the visible spectrum. Optoacoustic microscopy complements optical microscopy by imaging the absorption of light, but it is similarly limited by penetration depth. In this Review, we summarize progress in the development and applicability of optoacoustic mesoscopy (OPAM); that is, optoacoustic imaging with acoustic resolution and wide-bandwidth ultrasound detection. OPAM extends the capabilities of optical imaging beyond the depths accessible to optical and optoacoustic microscopy, and thus enables new applications. We explain the operational principles of OPAM, its placement as a bridge between optoacoustic microscopy and optoacoustic macroscopy, and its performance in the label-free visualization of tissue pathophysiology, such as inflammation, oxygenation, vascularization and angiogenesis. We also review emerging applications of OPAM in clinical and biological imaging.

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Fig. 1: Scanning implementations and operational regimes of OPAM.
Fig. 2: Effects of detector bandwidth, aperture and angle of acceptance, on the performance of optoacoustic imaging.

Dominik Soliman; panel c reproduced from ref. 32, Springer Nature Ltd.

Fig. 3: Skin imaging using OPAM.
Fig. 4: Optoacoustic endoscopy.

Andreas Buehler; panel f reproduced from ref. 159, The Optical Society; and panels g,h reproduced from ref. 157, Springer Nature Ltd.

Fig. 5: Translational imaging with OPAM.
Fig. 6: OPAM in development applications.


  1. 1.

    Helmchen, F. & Denk, W. Deep tissue two-photon microscopy. Nat. Methods 2, 932–940 (2005).

    CAS  PubMed  Google Scholar 

  2. 2.

    Theer, P., Hasan, M. T. & Denk, W. Two-photon imaging to a depth of 1000 μm in living brains by use of a Ti: Al 2 O 3 regenerative amplifier. Opt. Lett. 28, 1022–1024 (2003).

    CAS  PubMed  Google Scholar 

  3. 3.

    Smith, A. M., Mancini, M. C. & Nie, S. Second window for in vivo imaging. Nat. Nanotechnol. 4, 710 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Hong, G. et al. Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window. Nat. Commun. 5, 4206 (2014).

    CAS  PubMed  Google Scholar 

  5. 5.

    Vakoc, B. J. et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat. Med. 15, 1219–1223 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Drexler, W. et al. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat. Med. 7, 502 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Fujimoto, J. G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotechnol. 21, 1361 (2003).

    CAS  PubMed  Google Scholar 

  8. 8.

    Čižmár, T., Mazilu, M. & Dholakia, K. In situ wavefront correction and its application to micromanipulation. Nat. Photon. 4, 388–394 (2010).

    Google Scholar 

  9. 9.

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

    CAS  Google Scholar 

  10. 10.

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

    CAS  Google Scholar 

  11. 11.

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

    CAS  Google Scholar 

  12. 12.

    Ertürk, A. et al. Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat. Prot. 7, 1983 (2012).

    Google Scholar 

  13. 13.

    Hama, H. et al. ScaleS: an optical clearing palette for biological imaging. Nat. Neurosci. 18, 1518 (2015).

    CAS  PubMed  Google Scholar 

  14. 14.

    Dodt, H.-U. et al. Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat. Methods 4, 331 (2007).

    CAS  PubMed  Google Scholar 

  15. 15.

    Farkas, D. L. Invention and commercialization in optical bioimaging. Nat. Biotechnol. 21, 1269–1271 (2003).

    CAS  PubMed  Google Scholar 

  16. 16.

    Weissleder, R. & Pittet, M. J. Imaging in the era of molecular oncology. Nature 452, 580–589 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Vinegoni, C., Pitsouli, C., Razansky, D., Perrimon, N. & Ntziachristos, V. In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography. Nat. Methods 5, 45 (2008).

    CAS  PubMed  Google Scholar 

  18. 18.

    Sharpe, J. et al. Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296, 541–545 (2002).

    CAS  PubMed  Google Scholar 

  19. 19.

    Ntziachristos, V., Ripoll, J., Wang, L. V. & Weissleder, R. Looking and listening to light: the evolution of whole-body photonic imaging. Nat. Biotechnol. 23, 313–320 (2005).

    CAS  PubMed  Google Scholar 

  20. 20.

    Weissleder, R. A clearer vision for in vivo imaging. Nat. Biotechnol. 19, 316–316 (2001).

    CAS  PubMed  Google Scholar 

  21. 21.

    Maugh, T. H. Photoacoustic spectroscopy: New uses for an old technique. Science 188, 38–39 (1975).

    PubMed  Google Scholar 

  22. 22.

    Rosencwaig, A. & Gersho, A. Theory of the photoacoustic effect with solids. J. Appl. Physics 47, 64–69 (1976).

    Google Scholar 

  23. 23.

    Taruttis, A. & Ntziachristos, V. Advances in real-time multispectral optoacoustic imaging and its applications. Nat. Photon. 9, 219–227 (2015).

    CAS  Google Scholar 

  24. 24.

    Taruttis, A., van Dam, G. M. & Ntziachristos, V. Mesoscopic and macroscopic optoacoustic imaging of cancer. Cancer Res. 75, 1548–1559 (2015).

    CAS  PubMed  Google Scholar 

  25. 25.

    Wang, L. V. & Yao, J. A practical guide to photoacoustic tomography in the life sciences. Nat. Methods 13, 627 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Maslov, K., Zhang, H. F., Hu, S. & Wang, L. V. Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries. Opt. Lett. 33, 929–931 (2008).

    PubMed  Google Scholar 

  28. 28.

    Yao, J., Maslov, K. I., Zhang, Y., Xia, Y. & Wang, L. V. Label-free oxygen-metabolic photoacoustic microscopy in vivo. J. Biomed. Opt. 16, 076003 (2011).

    PubMed  PubMed Central  Google Scholar 

  29. 29.

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

    CAS  PubMed  Google Scholar 

  30. 30.

    Strohm, E. M., Berndl, E. S. L. & Kolios, M. C. Probing Red Blood Cell Morphology Using High-Frequency Photoacoustics. Biophys. J. 105, 59–67 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Strohm, E. M., Berndl, E. S. L. & Kolios, M. C. High frequency label-free photoacoustic microscopy of single cells. Photoacoustics 1, 49–53 (2013).

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Aguirre, J. S. et al. Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy. Nat. Biomed. Eng. 1, 0068 (2017).

    Google Scholar 

  33. 33.

    Alanentalo, T. et al. High-resolution three-dimensional imaging of islet-infiltrate interactions based on optical projection tomography assessments of the intact adult mouse pancreas. J. Biomed. Opt. 13, 054070 (2008).

    PubMed  Google Scholar 

  34. 34.

    Piras, D., Xia, W., Steenbergen, W., van Leeuwen, T. G. & Manohar, S. Photoacoustic imaging of the breast using the twente photoacoustic mammoscope: present status and future perspectives. IEEE J. Quantum Elect. 16, 730–739 (2010).

    CAS  Google Scholar 

  35. 35.

    Diot, G. et al. Multispectral optoacoustic tomography (MSOT) of human breast cancer. Clin. Cancer Res. 23, 6912–6922 (2017).

    CAS  PubMed  Google Scholar 

  36. 36.

    Oraevsky, A. et al. Full-view 3D imaging system for functional and anatomical screening of the breast. in Proc. SPIE 10494 https://doi.org/10.1117/12.2318802 (2018).

  37. 37.

    Knieling, F. et al. Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity. New Engl. J. Med. 376, 1292–1294 (2017).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Reber, J. et al. Non-invasive measurement of brown fat metabolism based on optoacoustic imaging of hemoglobin gradients. Cell Metab. 27, 689–701 (2018).

    CAS  PubMed  Google Scholar 

  39. 39.

    Weber, J., Beard, P. C. & Bohndiek, S. E. Contrast agents for molecular photoacoustic imaging. Nat. Methods 13, 639–650 (2016).

    CAS  PubMed  Google Scholar 

  40. 40.

    Xu, M. & Wang, L. V. Photoacoustic imaging in biomedicine. Rev. Sci. Instrum. 77, 041101 (2006).

    Google Scholar 

  41. 41.

    Li, M.-L., Zhang, H. F., Maslov, K., Stoica, G. & Wang, L. V. Improved in vivo photoacoustic microscopy based on a virtual-detector concept. Opt. Lett. 31, 474–476 (2006).

    PubMed  Google Scholar 

  42. 42.

    Westervelt, P. J. & Larson, R. S. Laser‐excited broadside array. J. Acoust. Soc. Am. 54, 121–122 (1973).

    Google Scholar 

  43. 43.

    Diebold, G., Sun, T. & Khan, M. Photoacoustic monopole radiation in one, two, and three dimensions. Phys. Rev. Lett. 67, 3384 (1991).

    CAS  PubMed  Google Scholar 

  44. 44.

    Ntziachristos, V. & Razansky, D. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chemical reviews 110, 2783–2794 (2010).

    CAS  PubMed  Google Scholar 

  45. 45.

    Xia, J., Yao, J. & Wang, L. V. Photoacoustic tomography: principles and advances. Electromag. Waves 147, 1 (2014).

    Google Scholar 

  46. 46.

    Deán-Ben, X. L. & Razansky, D. On the link between the speckle free nature of optoacoustics and visibility of structures in limited-view tomography. Photoacoustics 4, 133–140 (2016).

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Omar, M., Gateau, J. & Ntziachristos, V. Raster-scan optoacoustic mesoscopy in the 25–125 MHz range. Opt. Lett. 38, 2472–2474 (2013).

    PubMed  Google Scholar 

  48. 48.

    Omar, M., Soliman, D., Gateau, J. & Ntziachristos, V. Ultrawideband reflection-mode optoacoustic mesoscopy. Opt. Lett. 39, 3911–3914 (2014).

    PubMed  Google Scholar 

  49. 49.

    Laufer, J. et al. In vivo photoacoustic imaging of mouse embryos. J. Biomed. Opt. 17, 061220 (2012).

    PubMed  Google Scholar 

  50. 50.

    Jathoul, A. P. et al. Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter. Nat. Photon. (2015).

  51. 51.

    Park, J. et al. Delay-multiply-and-sum-based synthetic aperture focusing in photoacoustic microscopy. J. Biomed. Opt. 21, 036010 (2016).

    Google Scholar 

  52. 52.

    Laufer, J., Zhang, E., Raivich, G. & Beard, P. Three-dimensional noninvasive imaging of the vasculature in the mouse brain using a high resolution photoacoustic scanner. Appl. Opt. 48, 299–306 (2009).

    Google Scholar 

  53. 53.

    Zhang, E. Z. et al. Multimodal photoacoustic and optical coherence tomography scanner using an all optical detection scheme for 3D morphological skin imaging. Biomed. Opt. Exp. 2, 2202–2215 (2011).

    Google Scholar 

  54. 54.

    Aguirre, J. et al. Broadband mesoscopic optoacoustic tomography reveals skin layers. Opt. Lett. 39, 6297–6300 (2014).

    PubMed  Google Scholar 

  55. 55.

    Gateau, J., Chekkoury, A. & Ntziachristos, V. High-resolution optoacoustic mesoscopy with a 24 MHz multidetector translate-rotate scanner. J. Biomed. Opt. 18, 106005 (2013).

    PubMed  Google Scholar 

  56. 56.

    Vionnet, L. et al. 24-MHz scanner for optoacoustic imaging of skin and burn. IEEE Trans. Med. Imag. 33, 535–545 (2014).

    Google Scholar 

  57. 57.

    Zemp, R., Song, L., Bitton, R., Shung, K. & Wang, L. Realtime photoacoustic microscopy of murine cardiovascular dynamics. Opt. Exp. 16, 18551–18556 (2008).

    CAS  Google Scholar 

  58. 58.

    Wang, L., Maslov, K., Xing, W., Garcia-Uribe, A. & Wang, L. V. Video-rate functional photoacoustic microscopy at depths. J. Biomed. Opt. 17, 106007 (2012).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Zhang, H. F., Maslov, K., Stoica, G. & Wang, L. V. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nat. Biotechnol. 24, 848 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Fiolka, R., Wicker, K., Heintzmann, R. & Stemmer, A. Simplified approach to diffraction tomography in optical microscopy. Opt. Exp. 17, 12407–12417 (2009).

    CAS  Google Scholar 

  61. 61.

    Wicker, K., Mandula, O., Best, G., Fiolka, R. & Heintzmann, R. Phase optimisation for structured illumination microscopy. Opt. Exp. 21, 2032–2049 (2013).

    Google Scholar 

  62. 62.

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

    CAS  PubMed  Google Scholar 

  63. 63.

    Manley, S. et al. High-density mapping of single-molecule trajectories with photoactivated localization microscopy. Nat. Methods 5, 155–157 (2008).

    CAS  PubMed  Google Scholar 

  64. 64.

    Prevedel, R. et al. Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy. Nat. Methods 11, 727–730 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Gustafsson, M. G. Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J. Microsc. 198, 82–87 (2000).

    CAS  PubMed  Google Scholar 

  66. 66.

    Kim, T. et al. White-light diffraction tomography of unlabelled live cells. Nat. Photon. 8, 256–263 (2014).

    CAS  Google Scholar 

  67. 67.

    Keller, P. J. Imaging morphogenesis: technological advances and biological insights. Science 340, 1234168 (2013).

    PubMed  Google Scholar 

  68. 68.

    Razansky, D. et al. Multispectral opto-acoustic tomography of deep-seated fluorescent proteins. in vivo. Nat. Photon. 3, 412–417 (2009).

    CAS  Google Scholar 

  69. 69.

    Gateau, J., Caballero, M. Á. A., Dima, A. & Ntziachristos, V. Three‐dimensional optoacoustic tomography using a conventional ultrasound linear detector array: Whole‐body tomographic system for small animals. Med. Phys. 40 (2013).

  70. 70.

    Szabo, T. L. Diagnostic ultrasound imaging: inside out (Acad. Press, 2004).

  71. 71.

    Cobbold, R. S. Foundations of biomedical ultrasound (Oxford Univ. Press, 2006).

  72. 72.

    Zhang, E. Z. & Beard, P. C. A miniature all-optical photoacoustic imaging probe. in Proc. SPIE 7899 https://doi.org/10.1117/12.874883 (2011).

  73. 73.

    Nuster, R. et al. Hybrid photoacoustic and ultrasound section imaging with optical ultrasound detection. J. Biophoton. 6, 549–559 (2013).

    Google Scholar 

  74. 74.

    Deán-Ben, X. L., Razansky, D. & Ntziachristos, V. The effects of acoustic attenuation in optoacoustic signals. Phys. Med. Biol. 56, 6129 (2011).

    PubMed  Google Scholar 

  75. 75.

    Schwarz, M. S. et al. Optoacoustic dermoscopy of the human skin: tuning excitation energy for optimal detection bandwidth with fast and deep imaging in vivo. IEEE Trans. Med. Imaging 36, 1287–1296 (2017).

    PubMed  Google Scholar 

  76. 76.

    Laufer, J. et al. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy. J. Biomed. Opt. 17, 056016 (2012).

    PubMed  Google Scholar 

  77. 77.

    Wissmeyer, G., Soliman, D., Shnaiderman, R., Rosenthal, A. & Ntziachristos, V. All-optical optoacoustic microscope based on wideband pulse interferometry. Opt. Lett. 41, 1953–1956 (2016).

    PubMed  Google Scholar 

  78. 78.

    Rosenthal, A. et al. Sensitive interferometric detection of ultrasound for minimally invasive clinical imaging applications. Laser Photon. Rev. 8, 450–457 (2014).

    Google Scholar 

  79. 79.

    Schwarz, M., Buehler, A. & Ntziachristos, V. Isotropic high resolution optoacoustic imaging with linear detector arrays in bi‐directional scanning. J. Biophoton. 8, 60–70 (2015).

    Google Scholar 

  80. 80.

    Chekkoury, A. et al. Optical mesoscopy without the scatter: broadband multispectral optoacoustic mesoscopy. Biomed. Opt. Exp. 6, 3134–3148 (2015).

    CAS  Google Scholar 

  81. 81.

    Rebling, J., Warshavski, O., Meynier, C. & Razansky, D. Optoacoustic characterization of broadband directivity patterns of capacitive micromachined ultrasonic transducers. J. Biomed. Opt. 22, 041005 (2017).

    Google Scholar 

  82. 82.

    Oraevsky, A. A. & Karabutov, A. A. Ultimate sensitivity of time-resolved optoacoustic detection. in Proc. SPIE 3916, 228–239 (2000).

  83. 83.

    Zhang, E., Laufer, J. & Beard, P. Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues. Appl. Opt. 47, 561–577 (2008).

    CAS  PubMed  Google Scholar 

  84. 84.

    Beard, P. C., Hurrell, A. M. & Mills, T. N. Characterization of a polymer film optical fiber hydrophone for use in the range 1 to 20 MHz: A comparison with PVDF needle and membrane hydrophones. IEEE T. Ultrason. Ferr. 47, 256–264 (2000).

    CAS  Google Scholar 

  85. 85.

    Maswadi, S. M. et al. All-optical optoacoustic microscopy based on probe beam deflection technique. Photoacoustics 4, 91–101 (2016).

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Paltauf, G., Schmidt-Kloiber, H., Köstli, K. & Frenz, M. Optical method for two-dimensional ultrasonic detection. Appl. Phys. Lett. 75, 1048–1050 (1999).

    CAS  Google Scholar 

  87. 87.

    Omar, M. et al. Optical imaging of post-embryonic zebrafish using multi orientation raster scan optoacoustic mesoscopy. Light Sci. Appl. 6, e16186 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Xu, M. & Wang, L. V. Universal back-projection algorithm for photoacoustic computed tomography. Phys. Rev. E 71, 016706 (2005).

    Google Scholar 

  89. 89.

    Kostli, K. et al. Optoacoustic imaging using a three-dimensional reconstruction algorithm. IEEE J. Sel. Top. Quant. 7, 918–923 (2001).

    CAS  Google Scholar 

  90. 90.

    Karaman, M., Li, P.-C. & O’Donnell, M. Synthetic aperture imaging for small scale systems. IEEE T. Ultrason. Ferr. 42, 429–442 (1995).

    Google Scholar 

  91. 91.

    Köstli, K. P. & Beard, P. C. Two-dimensional photoacoustic imaging by use of Fourier-transform image reconstruction and a detector with an anisotropic response. Appl. Opt. 42, 1899–1908 (2003).

    PubMed  Google Scholar 

  92. 92.

    Oraevsky, A. A., Andreev, V. G., Karabutov, A. A. & Esenaliev, R. O. Two-dimensional optoacoustic tomography: transducer array and image reconstruction algorithm. in Proc. SPIE 3601 Laser Tissue Interaction X. https://doi.org/10.1117/12.350007 (1999).

  93. 93.

    Kruger, R. A., Liu, P., Fang, Y. & Appledorn, C. R. Photoacoustic ultrasound (PAUS)—reconstruction tomography. Med. Phys. 22, 1605–1609 (1995).

    CAS  PubMed  Google Scholar 

  94. 94.

    Rosenthal, A., Razansky, D. & Ntziachristos, V. Fast semi-analytical model-based acoustic inversion for quantitative optoacoustic tomography. IEEE T. Med. Imag. 29, 1275–1285 (2010).

    Google Scholar 

  95. 95.

    Caballero, M. Á. A., Rosenthal, A., Gateau, J., Razansky, D. & Ntziachristos, V. Model-based optoacoustic imaging using focused detector scanning. Opt. Lett. 37, 4080–4082 (2012).

    Google Scholar 

  96. 96.

    Dean-Ben, X. L., Buehler, A., Ntziachristos, V. & Razansky, D. Accurate model-based reconstruction algorithm for three-dimensional optoacoustic tomography. IEEE T. Med. Imag. 31, 1922–1928 (2012).

    Google Scholar 

  97. 97.

    Aguirre, J. et al. A low memory cost model based reconstruction algorithm exploiting translational symmetry for photoacoustic microscopy. Biomed. Opt. Exp. 4, 2813–2827 (2013).

    Google Scholar 

  98. 98.

    Mohajerani, P., Tzoumas, S., Rosenthal, A. & Ntziachristos, V. Optical and optoacoustic model-based tomography: Theory and current challenges for deep tissue imaging of optical contrast. IEEE Signal Proc. Mag. 32, 88–100 (2015).

    Google Scholar 

  99. 99.

    Anastasio, M. A., Zhang, J., Modgil, D. & La Rivière, P. J. Application of inverse source concepts to photoacoustic tomography. Inverse Problems 23, S21 (2007).

    Google Scholar 

  100. 100.

    Huang, C., Wang, K., Nie, L., Wang, L. V. & Anastasio, M. A. Full-wave iterative image reconstruction in photoacoustic tomography with acoustically inhomogeneous media. IEEE T. Med. Imag. 32, 1097–1110 (2013).

    Google Scholar 

  101. 101.

    Anastasio, M. A. et al. Half-time image reconstruction in thermoacoustic tomography. IEEE T. Med. Imag. 24, 199–210 (2005).

    Google Scholar 

  102. 102.

    La Rivière, P. J., Zhang, J. & Anastasio, M. A. Image reconstruction in optoacoustic tomography for dispersive acoustic media. Opt. Lett. 31, 781–783 (2006).

    PubMed  Google Scholar 

  103. 103.

    Wang, K. & Anastasio, M. A. in Handbook of Mathematical Methods in Imaging 781–815 (Springer, New York, 2011).

  104. 104.

    Wang, K., Su, R., Oraevsky, A. A. & Anastasio, M. A. Investigation of iterative image reconstruction in three-dimensional optoacoustic tomography. Phys. Med. Biol. 57, 5399 (2012).

    PubMed  PubMed Central  Google Scholar 

  105. 105.

    Cox, B. T., Arridge, S. R., Köstli, K. P. & Beard, P. C. Two-dimensional quantitative photoacoustic image reconstruction of absorption distributions in scattering media by use of a simple iterative method. Appl. Opt. 45, 1866–1875 (2006).

    PubMed  Google Scholar 

  106. 106.

    Tzoumas, S. et al. Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues. Nat. Commun. 7, 12121 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Cox, B., Laufer, J. G., Arridge, S. R. & Beard, P. C. Quantitative spectroscopic photoacoustic imaging: a review. J. Biomed. Opt. 17, 061202 (2012).

    PubMed  Google Scholar 

  108. 108.

    Tzoumas, S., Deliolanis, N., Morscher, S. & Ntziachristos, V. Unmixing molecular agents from absorbing tissue in multispectral optoacoustic tomography. IEEE T. Med. Imag. 33, 48–60 (2014).

    Google Scholar 

  109. 109.

    Schwarz, M., Buehler, A., Aguirre, J. & Ntziachristos, V. Three‐dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin. in vivo. J. Biophoton. 9, 55–60 (2016).

    CAS  Google Scholar 

  110. 110.

    Mohajerani, P., Kellnberger, S. & Ntziachristos, V. Frequency domain optoacoustic tomography using amplitude and phase. Photoacoustics 2, 111–118 (2014).

    PubMed  PubMed Central  Google Scholar 

  111. 111.

    Kellnberger, S., Deliolanis, N. C., Queirós, D., Sergiadis, G. & Ntziachristos, V. In vivo frequency domain optoacoustic tomography. Opt. Lett. 37, 3423–3425 (2012).

    PubMed  Google Scholar 

  112. 112.

    Telenkov, S., Mandelis, A., Lashkari, B. & Forcht, M. Frequency-domain photothermoacoustics: Alternative imaging modality of biological tissues. J. Appl. Phys. 105, 102029 (2009).

    Google Scholar 

  113. 113.

    VanderLaan, D., Karpiouk, A., Yeager, D. & Emelianov, S. Real-time intravascular ultrasound and photoacoustic imaging. IEEE T. Ultrason. Ferr. 64, 141–149 (2016).

    Google Scholar 

  114. 114.

    Wu, M. et al. Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second. Biomed. Optics Exp. 8, 943–953 (2017).

    CAS  Google Scholar 

  115. 115.

    Beziere, N. et al. Optoacoustic imaging and staging of inflammation in a murine model of arthritis. Arthritis Rheumatol. 66, 2071–2078 (2014).

    CAS  PubMed  Google Scholar 

  116. 116.

    Mallidi, S., Luke, G. P. & Emelianov, S. Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance. Trends Biotechnol. 29, 213–221 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Liu, Y., Nie, L. & Chen, X. Photoacoustic molecular imaging: from multiscale biomedical applications towards early-stage theranostics. Trends Biotechnol. 34, 420–433 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Beziere, N. et al. Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT). Biomaterials 37, 415–424 (2015).

    CAS  PubMed  Google Scholar 

  119. 119.

    Lozano, N., Al-Ahmady, Z. S., Beziere, N. S., Ntziachristos, V. & Kostarelos, K. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent. Int. J. Pharm. 482, 2–10 (2015).

    CAS  PubMed  Google Scholar 

  120. 120.

    Wilson, K., Homan, K. & Emelianov, S. Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging. Nat. Commun. 3, 618 (2012).

    PubMed  Google Scholar 

  121. 121.

    Luke, G. P., Yeager, D. & Emelianov, S. Y. Biomedical applications of photoacoustic imaging with exogenous contrast agents. Ann. Biomed. Eng. 40, 422–437 (2012).

    PubMed  Google Scholar 

  122. 122.

    Copland, J. A. et al. Bioconjugated gold nanoparticles as a molecular based contrast agent: implications for imaging of deep tumors using optoacoustic tomography. Mol. Imag. Biol. 6, 341–349 (2004).

    Google Scholar 

  123. 123.

    Conjusteau, A. et al. Metallic nanoparticles as optoacoustic contrast agents for medical imaging. In Proc. SPIE 6086 Photons Plus Ultrasound: Imaging and Sensing https://doi.org/10.1117/12.658065 (2006).

  124. 124.

    Gindy, M. E. & Prud’homme, R. K. Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opin. Drug Del. 6, 865–878 (2009).

    CAS  Google Scholar 

  125. 125.

    Haedicke, K. et al. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging. Photoacoustics 6, 1–8 (2017).

    PubMed  PubMed Central  Google Scholar 

  126. 126.

    Stritzker, J. et al. Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer. Proc. Natl Acad. Sci. USA 110, 3316–3320 (2013).

    CAS  PubMed  Google Scholar 

  127. 127.

    Paproski, R. J., Forbrich, A. E., Wachowicz, K., Hitt, M. M. & Zemp, R. J. Tyrosinase as a dual reporter gene for both photoacoustic and magnetic resonance imaging. Biomed. Opt. Exp. 2, 771–780 (2011).

    CAS  Google Scholar 

  128. 128.

    Stiel, A. C. et al. High-contrast imaging of reversibly switchable fluorescent proteins via temporally unmixed multispectral optoacoustic tomography. Opt. Lett. 40, 367–370 (2015).

    CAS  PubMed  Google Scholar 

  129. 129.

    Yao, J. et al. Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe. Nat. Methods 13, 67–73 (2016).

    CAS  PubMed  Google Scholar 

  130. 130.

    Bost, W., Lemor, R. & Fournelle, M. Optoacoustic Imaging of subcutaneous microvasculature with a class one laser. IEEE T. Med. Imag. 33, 1900–1904 (2014).

    Google Scholar 

  131. 131.

    Kirillin, M., Perekatova, V., Turchin, I. & Subochev, P. Fluence compensation in raster-scan optoacoustic angiography. Photoacoustics 8, 59–67 (2017).

    PubMed  PubMed Central  Google Scholar 

  132. 132.

    Zhang, E., Laufer, J., Pedley, R. & Beard, P. In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy. Phys. Med. Biol. 54, 1035 (2009).

    CAS  PubMed  Google Scholar 

  133. 133.

    Aguirre, J. et al. The potential of photoacoustic microscopy as a tool to characterize the in vivo degradation of surgical sutures. Biomed. Opt. Exp. 5, 2856–2869 (2014).

    Google Scholar 

  134. 134.

    Nam, S. Y., Chung, E., Suggs, L. J. & Emelianov, S. Y. Combined ultrasound and photoacoustic imaging to noninvasively assess burn injury and selectively monitor a regenerative tissue-engineered construct. Tissue Eng. Part C Me. 21, 557–566 (2015).

    CAS  Google Scholar 

  135. 135.

    Aizawa, K., Sato, S., Saitoh, D., Ashida, H. & Obara, M. Photoacoustic monitoring of burn healing process in rats. J. Biomed. Opt. 13, 064020 (2008).

    PubMed  Google Scholar 

  136. 136.

    Ida, T. et al. Real-time photoacoustic imaging system for burn diagnosis. J. Biomed. Opt. 19, 086013 (2014).

    PubMed  Google Scholar 

  137. 137.

    Zhou, Y., Xing, W., Maslov, K. I., Cornelius, L. A. & Wang, L. V. Handheld photoacoustic microscopy to detect melanoma depth in vivo. Opt. Lett. 39, 4731–4734 (2014).

    PubMed  PubMed Central  Google Scholar 

  138. 138.

    Zhou, Y. et al. Handheld photoacoustic probe to detect both melanoma depth and volume at high speed in vivo. J. Biophoton. 8, 961–967 (2015).

    Google Scholar 

  139. 139.

    Welzel, J., Lankenau, E., Birngruber, R. & Engelhardt, R. Optical coherence tomography of the human skin. J. Am. Acad. Dermatol. 37, 958–963 (1997).

    CAS  PubMed  Google Scholar 

  140. 140.

    Welzel, J. Optical coherence tomography in dermatology: a review. Skin Re. Technol. 7, 1–9 (2001).

    CAS  Google Scholar 

  141. 141.

    Zhao, Y. et al. Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity. Opt. Lett. 25, 114–116 (2000).

    CAS  PubMed  Google Scholar 

  142. 142.

    Vogt, M. & Ermert, H. Development and evaluation of a high-frequency ultrasound-based system for in vivo strain imaging of the skin. IEEE T. Ultrason. Ferr. 52, 375–385 (2005).

    Google Scholar 

  143. 143.

    Turnbull, D. H. et al. A 40–100 MHz B-scan ultrasound backscatter microscope for skin imaging. Ultrasound Med. Biol. 21, 79–88 (1995).

    CAS  PubMed  Google Scholar 

  144. 144.

    Serup, J., Keiding, J., Fullerton, A., Gniadecka, M. & Gniadecki, R. in Handbook of non-invasive methods and the skin. (eds Serup, J., Jemec, G. B. E. & Grove, G. L.) 473–491 (Taylor & Francis, 2006).

  145. 145.

    Mintz, G. S. et al. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). J. Am. Coll. Cardiol. 37, 1478–1492 (2001).

    CAS  PubMed  Google Scholar 

  146. 146.

    Nair, A. et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 106, 2200–2206 (2002).

    PubMed  Google Scholar 

  147. 147.

    Jang, I.-K. et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J. Am. Coll. Cardiol. 39, 604–609 (2002).

    PubMed  Google Scholar 

  148. 148.

    VanderLaan, D., Karpiouk, A. B., Yeager, D. & Emelianov, S. Real-time intravascular ultrasound and photoacoustic imaging. IEEE T. Ultrason. Ferr. 64, 141–149 (2017).

    Google Scholar 

  149. 149.

    Jansen, K. et al. Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis. J. Biomed. Opt. 19, 026006 (2014).

    PubMed  Google Scholar 

  150. 150.

    Wang, P. et al. High-speed intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque enabled by a 2-kHz barium nitrite raman laser. Sci. Rep. 4, 6889 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Jansen, K., Wu, M., van der Steen, A. F. & van Soest, G. Lipid detection in atherosclerotic human coronaries by spectroscopic intravascular photoacoustic imaging. Opt. Exp. 21, 21472–21484 (2013).

    Google Scholar 

  152. 152.

    Wang, B. et al. In vivo intravascular ultrasound-guided photoacoustic imaging of lipid in plaques using an animal model of atherosclerosis. Ultrasound Med. Biol. 38, 2098–2103 (2012).

    PubMed  PubMed Central  Google Scholar 

  153. 153.

    Zhang, J., Yang, S., Ji, X., Zhou, Q. & Xing, D. Characterization of lipid-rich aortic plaques by intravascular photoacoustic tomography. J. Am. Coll. Cardiol. 64, 385–390 (2014).

    CAS  PubMed  Google Scholar 

  154. 154.

    Hui, J. et al. Real-time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque in human coronary artery at 16 frames per second. Sci. Rep. 7, 1417 (2017).

    PubMed  PubMed Central  Google Scholar 

  155. 155.

    Ansari, R., Beard, P. C., Zhang, E. Z. & Desjardins, A. E. Photoacoustic endoscopy probe using a coherent fibre-optic bundle and Fabry-Pérot ultrasound sensor. In Proc. SPIE 9708 Photons Plus Ultrasound: Imaging and Sensing https://doi.org/10.1117/12.2209687 (2016).

  156. 156.

    He, H., Wissmeyer, G., Ovsepian, S. V., Buehler, A. & Ntziachristos, V. Hybrid optical and acoustic resolution optoacoustic endoscopy. Optics Letters 41, 2708–2710 (2016).

    PubMed  Google Scholar 

  157. 157.

    Yang, J.-M. et al. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat. Med. 18, 1297–1302 (2012).

    CAS  PubMed  Google Scholar 

  158. 158.

    Yang, J. M. et al. Three-dimensional photoacoustic endoscopic imaging of the rabbit esophagus. PloS ONE 10, e0120269 (2015).

    PubMed  PubMed Central  Google Scholar 

  159. 159.

    Yang, J.-M. et al. Photoacoustic endoscopy. Opt. Lett. 34, 1591–1593 (2009).

    PubMed  PubMed Central  Google Scholar 

  160. 160.

    He, H., Buehler, A. & Ntziachristos, V. Optoacoustic endoscopy with curved scanning. Opt. Lett. 40, 4667–4670 (2015).

    PubMed  Google Scholar 

  161. 161.

    Chen, S.-L., Ling, T., Baac, H. W. & Guo, L. J. Photoacoustic endoscopy using polymer microring resonators. In Proc. SPIE 7899, Photons Plus Ultrasound: Imaging and Sensing https://doi.org/10.1117/12.874205 (2011).

  162. 162.

    Yuan, Y., Yang, S. & Xing, D. Preclinical photoacoustic imaging endoscope based on acousto-optic coaxial system using ring transducer array. Opt. Lett. 35, 2266–2268 (2010).

    PubMed  Google Scholar 

  163. 163.

    Barendse, R. et al. Endoscopic mucosal resection vs transanal endoscopic microsurgery for the treatment of large rectal adenomas. Colorectal Dis. 14, 191–196 (2012).

    Google Scholar 

  164. 164.

    Soetikno, R. M., Gotoda, T., Nakanishi, Y. & Soehendra, N. Endoscopic mucosal resection. Gastrointest. Endosc. 57, 567–579 (2003).

    PubMed  Google Scholar 

  165. 165.

    Yang, Y. et al. Integrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterization. Biomed. Opt. Exp. 2, 2551–2561 (2011).

    Google Scholar 

  166. 166.

    Omar, M., Schwarz, M., Soliman, D., Symvoulidis, P. & Ntziachristos, V. Pushing the optical imaging limits of cancer with multi-frequency-band raster-scan optoacoustic mesoscopy (RSOM). Neoplasia 17, 208–214 (2015).

    PubMed  PubMed Central  Google Scholar 

  167. 167.

    Chekkoury, A. et al. High-resolution multispectral optoacoustic tomography of the vascularization and constitutive hypoxemia of cancerous tumors. Neoplasia 18, 459–467 (2016).

    PubMed  PubMed Central  Google Scholar 

  168. 168.

    Ellenbroek, S. I. & Van Rheenen, J. Imaging hallmarks of cancer in living mice. Nat. Rev. Cancer 14, 406–418 (2014).

    CAS  PubMed  Google Scholar 

  169. 169.

    Kim, C. et al. In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. ACS Nano 4, 4559–4564 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. 170.

    Deán-Ben, X. L. et al. Functional optoacoustic neuro-tomography for scalable whole-brain monitoring of calcium indicators. Light Sci. Appl. 5, e16201 (2016).

    PubMed  PubMed Central  Google Scholar 

  171. 171.

    Deán-Ben, X. L. & Razansky, D. Adding fifth dimension to optoacoustic imaging: volumetric time-resolved spectrally enriched tomography. Light Sci. Appl. 3, e137 (2014).

    Google Scholar 

  172. 172.

    Stein, E. W., Maslov, K. & Wang, L. V. Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy. J. Biomed. Opt. 14, 020502 (2009).

    PubMed  PubMed Central  Google Scholar 

  173. 173.

    Stein, E. W., Maslov, K. & Wang, L. V. Noninvasive, in vivo imaging of the mouse brain using photoacoustic microscopy. J. Appl. Phys. 105, 102027 (2009).

    PubMed  PubMed Central  Google Scholar 

  174. 174.

    Johannes Rebling, J., Estrada, H., Zwack, M., Sela, G., Gottschalk, S., and Razansky, D., Hybrid ultrasound and dual-wavelength optoacoustic biomicroscopy for functional neuroimaging. In Proc. SPIE 10064, Photons Plus Ultrasound: Imaging and Sensing https://doi.org/10.1117/12.2250635 (2017).

  175. 175.

    Estrada, H., Turner, J., Kneipp, M. & Razansky, D. Real-time optoacoustic brain microscopy with hybrid optical and acoustic resolution. Laser Phys. Lett. 11, 045601 (2014).

    Google Scholar 

  176. 176.

    Liao, L.-D. et al. Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy. Neuroimage 52, 562–570 (2010).

    PubMed  Google Scholar 

  177. 177.

    Liao, L.-D. et al. Transcranial imaging of functional cerebral hemodynamic changes in single blood vessels using in vivo photoacoustic microscopy. J. Cerebr. Blood F. Met. 32, 938–951 (2012).

    CAS  Google Scholar 

  178. 178.

    Deng, Z., Wang, Z., Yang, X., Luo, Q. & Gong, H. In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy. J. Biomed. Opt. 17, 081415 (2012).

    PubMed  Google Scholar 

  179. 179.

    Yao, J. & Wang, L. V. Photoacoustic brain imaging: from microscopic to macroscopic scales. Neurophotonics 1, 011003–011003 (2014).

    PubMed Central  Google Scholar 

  180. 180.

    Wang, D., Wu, Y. & Xia, J. Review on photoacoustic imaging of the brain using nanoprobes. Neurophotonics 3, 010901–010901 (2016).

    PubMed  PubMed Central  Google Scholar 

  181. 181.

    Hu, S. Listening to the brain with photoacoustics. IEEE J. Sel. T. Quant. 22, 117–126 (2016).

    Google Scholar 

  182. 182.

    Kim, K. et al. Photoacoustic imaging of early inflammatory response using gold nanorods. Appl. Phys. Lett. 90, 223901 (2007).

    Google Scholar 

  183. 183.

    Ha, S., Carson, A., Agarwal, A., Kotov, N. A. & Kim, K. Detection and monitoring of the multiple inflammatory responses by photoacoustic molecular imaging using selectively targeted gold nanorods. Biomed. Opt. Exp. 2, 645–657 (2011).

    CAS  Google Scholar 

  184. 184.

    Seeger, M., Karlas, A., Soliman, D., Pelisek, J. & Ntziachristos, V. Multimodal optoacoustic and multiphoton microscopy of human carotid atheroma. Photoacoustics 4, 102–111 (2016).

    PubMed  PubMed Central  Google Scholar 

  185. 185.

    Estrada, H., Sobol, E., Baum, O. & Razansky, D. Hybrid optoacoustic and ultrasound biomicroscopy monitors’ laser-induced tissue modifications and magnetite nanoparticle impregnation. Laser Phys. Lett. 11, 125601 (2014).

    Google Scholar 

  186. 186.

    Lin, H. C. A. et al. Selective plane illumination optical and optoacoustic microscopy for postembryonic imaging. Laser Photon. Rev. 9, 29–34 (2015).

    Google Scholar 

  187. 187.

    Soliman, D., Tserevelakis, G. J., Omar, M. & Ntziachristos, V. Combining microscopy with mesoscopy using optical and optoacoustic label-free modes. Sci. Rep. 5, 12902 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. 188.

    Tserevelakis, G. J., Soliman, D., Omar, M. & Ntziachristos, V. Hybrid multiphoton and optoacoustic microscope. Opt. Lett. 39, 1819–1822 (2014).

    PubMed  Google Scholar 

  189. 189.

    Li, G., Li, L., Zhu, L., Xia, J. & Wang, L. V. Multiview Hilbert transformation for full-view photoacoustic computed tomography using a linear array. J. Biomed. Opt. 20, 066010 (2015).

    PubMed  PubMed Central  Google Scholar 

  190. 190.

    Harrison, T. et al. Combined photoacoustic and ultrasound biomicroscopy. Opt. Exp. 17, 22041–22046 (2009).

    CAS  Google Scholar 

  191. 191.

    Xi, L., Zhou, L. & Jiang, H. C-scan photoacoustic microscopy for in vivo imaging of Drosophila pupae. Appl. Phys. Lett. 101, 013702 (2012).

    Google Scholar 

  192. 192.

    Xie, B. et al. Optoacoustic detection of early therapy-induced tumor cell death using a targeted imaging agent. Clin. Cancer Res. 23, 6893–6903 (2017).

    CAS  PubMed  Google Scholar 

  193. 193.

    Tomaszewski, M. R. et al. Oxygen enhanced optoacoustic tomography (OE-OT) reveals vascular dynamics in murine models of prostate cancer. Theranostics 7, 2900 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. 194.

    Jose, J. et al. Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography. J. Biomed. Opt. 16, 096021 (2011).

    PubMed  Google Scholar 

  195. 195.

    Pramanik, M., Ku, G., Li, C. & Wang, L. V. Design and evaluation of a novel breast cancer detection system combining both thermoacoustic (TA) and photoacoustic (PA) tomography. Med. Phys. 35, 2218–2223 (2008).

    PubMed  PubMed Central  Google Scholar 

  196. 196.

    Kolkman, R. G. M. et al. Photoacoustic mammography laboratory prototype: imaging of breast tissue phantoms. J. Biomed. Opt. 9, 1172 (2004).

    Google Scholar 

  197. 197.

    Jose, J., Manohar, S., Kolkman, R. G., Steenbergen, W. & van Leeuwen, T. G. Imaging of tumor vasculature using Twente photoacoustic systems. J. Biophoton. 2, 701–717 (2009).

    CAS  Google Scholar 

  198. 198.

    Heijblom, M. et al. Imaging tumor vascularization for detection and diagnosis of breast cancer. Technol. Cancer Res. T. 10, 607–623 (2011).

    CAS  Google Scholar 

  199. 199.

    Heijblom, M. et al. Visualizing breast cancer using the Twente photoacoustic mammoscope: what do we learn from twelve new patient measurements? Opt. Exp. 20, 11582–11597 (2012).

    CAS  Google Scholar 

  200. 200.

    Gurka, M. K. et al. Identification of pancreatic tumors in vivo with ligand-targeted, pH responsive mesoporous silica nanoparticles by multispectral optoacoustic tomography. J. Control. Release 231, 60–67 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. 201.

    Valluru, K. S. & Willmann, J. K. Clinical photoacoustic imaging of cancer. Ultrasonography 35, 267 (2016).

    PubMed  PubMed Central  Google Scholar 

  202. 202.

    Stoffels, I. et al. Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging. Sci. Transl Med. 7, 317ra199 (2015).

    PubMed  Google Scholar 

  203. 203.

    Neuschmelting, V., Lockau, H., Ntziachristos, V., Grimm, J. & Kircher, M. F. Lymph node micrometastases and in-transit metastases from melanoma: in vivo detection with multispectral optoacoustic imaging in a mouse model. Radiology 280, 137–150 (2016).

    PubMed  PubMed Central  Google Scholar 

  204. 204.

    Waldner, M. J. et al. Multispectral optoacoustic tomography in Crohn’s disease: noninvasive imaging of disease activity. Gastroenterology 151, 238–240 (2016).

    PubMed  Google Scholar 

  205. 205.

    Knieling, F. et al. Multispectral optoacoustic tomography in Crohn’s disease — a first-in-human diagnostic clinical trial. J. Nuclear Med. 58, 379–379 (2017).

    Google Scholar 

  206. 206.

    Lev-Tov, H. Dive deep, stay focused! Sci. Transl Med. 9, eaan4292 (2017).

    PubMed  Google Scholar 

  207. 207.

    Allen, T. J., Hall, A., Dhillon, A. P., Owen, J. S. & Beard, P. C. Spectroscopic photoacoustic imaging of lipid-rich plaques in the human aorta in the 740 to 1400 nm wavelength range. J Biomed. Opt. 17, 061209 (2012).

    PubMed  Google Scholar 

  208. 208.

    Liotta, L. A., Steeg, P. S. & Stetler-Stevenson, W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64, 327–336 (1991).

    CAS  PubMed  Google Scholar 

  209. 209.

    Filonov, G. S. et al. Deep‐tissue photoacoustic tomography of a genetically encoded near‐infrared fluorescent probe. Angew. Chem. Int. Edit. 51, 1448–1451 (2012).

    CAS  Google Scholar 

  210. 210.

    Deán-Ben, X. L. & Razansky, D. Functional optoacoustic human angiography with handheld video rate three dimensional scanner. Photoacoustics 1, 68–73 (2013).

    PubMed  PubMed Central  Google Scholar 

  211. 211.

    Zabihian, B. et al. In vivo dual-modality photoacoustic and optical coherence tomography imaging of human dermatological pathologies. Biomed. Opt. Exp. 6, 3163–3178 (2015).

    Google Scholar 

  212. 212.

    Castelino, R. F., Hynes, M., Munding, C. E., Telenkov, S. & Foster, F. S. Combined frequency domain photoacoustic and ultrasound imaging for intravascular applications. Biomed. Opt. Exp. 7, 4441–4449 (2016).

    Google Scholar 

  213. 213.

    Ji, X., Xiong, K., Yang, S. & Xing, D. Intravascular confocal photoacoustic endoscope with dual-element ultrasonic transducer. Opt. Exp. 23, 9130–9136 (2015).

    CAS  Google Scholar 

  214. 214.

    Jansen, K., Van der Steen, A. F., Van Beusekom, H. M., Oosterhuis, J. W. & Van Soest, G. Intravascular photoacoustic imaging of human coronary atherosclerosis. Opt. Lett. 36, 597–599 (2011).

    PubMed  Google Scholar 

  215. 215.

    Karpiouk, A. B., Wang, B. & Emelianov, S. Y. Development of a catheter for combined intravascular ultrasound and photoacoustic imaging. Rev. Sci. Instrum. 81, 014901 (2010).

    PubMed  PubMed Central  Google Scholar 

  216. 216.

    Yang, J.-M. et al. A 2.5-mm diameter probe for photoacoustic and ultrasonic endoscopy. Opt. Exp. 20, 23944–23953 (2012).

    Google Scholar 

  217. 217.

    Subochev, P. et al. Simultaneous photoacoustic and optically mediated ultrasound microscopy: phantom study. Opt. Lett. 37, 4606–4608 (2012).

    CAS  PubMed  Google Scholar 

  218. 218.

    Subochev, P., Orlova, A., Shirmanova, M., Postnikova, A. & Turchin, I. Simultaneous photoacoustic and optically mediated ultrasound microscopy: an in vivo study. Biomed. Opt. Exp. 6, 631–638 (2015).

    Google Scholar 

  219. 219.

    Subochev, P., Fiks, I. & Frenz, M. Simultaneous triple-modality imaging of diffuse reflectance, optoacoustic pressure and ultrasonic scattering using an acoustic-resolution photoacoustic microscope: feasibility study. Laser Phys. Lett. 13, 025605 (2016).

    Google Scholar 

  220. 220.

    Subochev, P. Cost-effective imaging of optoacoustic pressure, ultrasonic scattering, and optical diffuse reflectance with improved resolution and speed. Opt. Lett. 41, 1006–1009 (2016).

    PubMed  Google Scholar 

  221. 221.

    Liu, M. et al. In vivo three dimensional dual wavelength photoacoustic tomography imaging of the far-red fluorescent protein E2-Crimson expressed in adult zebrafish. Biomed. Opt. Exp. 4, 1846–1855 (2013).

    Google Scholar 

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The authors would like to thank Chapin Rodriguez for proofreading the manuscript and for his valuable suggestions, and Luis Den Bean for his useful comments and suggestions. V.N. acknowledges funding from the Deutsche Forschungsgemeinschaft, Germany (Leibniz Prize 2013; NT 3/10-1), from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 687866 (INNODERM), and from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 732720 (ESOTRAC). The content of this manuscript reflects only the authors’ view, and the European commission is not responsible for any use that may be made of the information provided.

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Correspondence to Vasilis Ntziachristos.

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V.N. is a shareholder in iThera Medical GmbH, a company that commercializes optoacoustic mesoscopy. The company did not provide support for this work.

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Omar, M., Aguirre, J. & Ntziachristos, V. Optoacoustic mesoscopy for biomedicine. Nat Biomed Eng 3, 354–370 (2019). https://doi.org/10.1038/s41551-019-0377-4

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