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Depth resolved label-free multimodal optical imaging platform to study morpho-molecular composition of tissue

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  • Published: 27 October 2020
  • Volume 18, pages 997–1008, (2019)
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Photochemical & Photobiological Sciences Aims and scope Submit manuscript
Depth resolved label-free multimodal optical imaging platform to study morpho-molecular composition of tissue
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  • Marco Andreana1,
  • Ryan Sentosa1,
  • Mikael T. Erkkilä1,
  • Wolfgang Drexler1 &
  • …
  • Angelika Unterhuber1 

  • 249 Accesses

  • 10 Altmetric

  • 1 Mention

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Abstract

Multimodal imaging platforms offer a vast array of tissue information in a single image acquisition by combining complementary imaging techniques. By merging different systems, better tissue characterization can be achieved than is possible by the constituent imaging modalities alone. The combination of optical coherence tomography (OCT) with non-linear optical imaging (NLOI) techniques such as two-photon excited fluorescence (TPEF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) provides access to detailed information of tissue structure and molecular composition in a fast, label-free and non-invasive manner. We introduce a multimodal label-free approach for morphomolecular imaging and spectroscopy and validate the system in mouse skin demonstrating the potential of the system for colocalized acquisition of OCT and NLOI signals.

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  1. B. C. Wilson, M. Jermyn and F. Leblond, Challenges and opportunities in clinical translation of biomedical optical spectroscopy and imaging, J. Biomed. Opt., 2018, 23, 030901.

    Article  PubMed Central  Google Scholar 

  2. S. Yue, M. N. Slipchenko and J.-X. Cheng, Multimodal nonlinear optical microscopy, Laser Photonics Rev., 2011, 5, 496–512.

    Article  Google Scholar 

  3. C. P. Pfeffer, B. R. Olsen, F. Ganikhanov and F. Légaré, Multimodal nonlinear optical imaging of collagen arrays, J. Struct. Biol., 2008, 164, 140–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. A. Zoumi, A. Yeh and B. J. Tromberg, Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 11014–11019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. W. R. Zipfel, R. M. Williams and W. W. Webb, Nonlinear magic: multiphoton microscopy in the biosciences, Nat. Biotechnol., 2003, 21, 1369–1377.

    Article  CAS  PubMed  Google Scholar 

  6. F. Helmchen and W. Denk, Deep tissue two-photon microscopy, Nat. Methods, 2005, 2, 932–940.

    Article  CAS  PubMed  Google Scholar 

  7. C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin and X. S. Xie, Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy, Proc. Natl. Acad. Sci. U. S. A., 2005, 102, 16807–16812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. M. Ji, S. Lewis, S. Camelo-Piragua, S. H. Ramkissoon, M. Snuderl, S. Venneti, A. Fisher-Hubbard, M. Garrard, D. Fu, A. C. Wang, J. A. Heth, C. O. Maher, N. Sanai, T. D. Johnson, C. W. Freudiger, O. Sagher, X. S. Xie and D. A. Orringer, Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy, Sci. Transl. Med., 2015, 7, 309ra163–309ra163.

  9. D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb and C. Xu, Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue, Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 17598–17603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. J. Hou, J. Williams, E. L. Botvinick, E. O. Potma and B. J. Tromberg, Visualization of Breast Cancer Metabolism Using Multimodal Nonlinear Optical Microscopy of Cellular Lipids and Redox State, Cancer Res., 2018, 78, 2503–2512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. W. Denk, J. H. Strickler and W. W. Webb, Two-photon laser scanning fluorescence microscopy, Science, 1990, 248, 73–76.

    Article  CAS  PubMed  Google Scholar 

  12. W. Y. Sanchez, T. W. Prow, W. H. Sanchez, J. Grice and M. S. Roberts, Analysis of the metabolic deterioration of ex vivo skin from ischemic necrosis through the imaging of intracellular NAD(P)H by multiphoton tomography and fluorescence lifetime imaging microscopy, J. Biomed. Opt., 2010, 15, 046008.

    Article  PubMed  CAS  Google Scholar 

  13. M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan and B. J. Tromberg, In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin, Biophys. J., 2013, 104, 258–267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. G. Thomas, J. van Voskuilen, H. C. Gerritsen and H. J. Sterenborg, Advances and challenges in label-free nonlinear optical imaging using two-photon excitation fluorescence and second harmonic generation for cancer research, J. Photochem. Photobiol., B, 2014, 141, 128–138.

    Article  CAS  Google Scholar 

  15. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman and W. W. Webb, Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation, Proc. Natl. Acad. Sci. U. S. A., 2003, 100, 7075–7080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. K. Vishwanath and N. Ramanujam, in Encyclopedia of Analytical Chemistry, American Cancer Society, 2011.

  17. B.-G. Wang, K. König and K.-J. Halbhuber, Two-photon microscopy of deep intravital tissues and its merits in clinical research, J. Microsc., 2010, 238, 1–20.

    Article  CAS  PubMed  Google Scholar 

  18. M. Y. Berezin and S. Achilefu, Fluorescence lifetime measurements and biological imaging, Chem. Rev., 2010, 110, 2641–2684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher and R. K. Jain, Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation, Nat. Med., 2003, 9, 796–800.

    Article  CAS  PubMed  Google Scholar 

  20. F. S. Pavone and P. J. Campagnola, Second Harmonic Generation Imaging, CRC Press, 2013.

  21. I. Freund, M. Deutsch and A. Sprecher, Connective tissue polarity. Optical second-harmonic microscopy, crossedbeam summation, and small-angle scattering in rat-tail tendon, Biophys. J., 1986, 50, 693–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. M. Nuriya, J. Jiang, B. Nemet, K. B. Eisenthal and R. Yuste, Imaging membrane potential in dendritic spines, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 786–790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. O. Nadiarnykh, R. B. LaComb, M. A. Brewer and P. J. Campagnola, Alterations of the extracellular matrix in ovarian cancer studied by Second Harmonic Generation imaging microscopy, BMC Cancer, 2010, 10, 94.

    Article  PubMed  PubMed Central  Google Scholar 

  24. J. Sun, T. Shilagard, B. Bell, M. Motamedi and G. Vargas, In vivo multimodal nonlinear optical imaging of mucosal tissue, Opt. Express, 2004, 12, 2478–2486.

    Article  PubMed  Google Scholar 

  25. E. J. Gualda, G. Filippidis, G. Voglis, M. Mari, C. Fotakis and N. Tavernarakis, In vivo imaging of cellular structures in Caenorhabditis elegans by combined TPEF, SHG and THG microscopy, J. Microsc., 2008, 229, 141–150.

    Article  CAS  PubMed  Google Scholar 

  26. J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel and M. H. Nathanson, Multiphoton Imaging Can Be Used for Microscopic Examination of Intact Human Gastrointestinal Mucosa Ex Vivo, Clin. Gastroenterol. Hepatol., 2008, 6, 95–101.

    Article  PubMed  Google Scholar 

  27. J. Yan, G. Chen, J. Chen, N. Liu, S. Zhuo, H. Yu and M. Ying, A pilot study of using multiphoton microscopy to diagnose gastric cancer, Surg. Endosc., 2011, 25, 1425–1430.

    Article  PubMed  Google Scholar 

  28. M. D. Duncan, J. Reintjes and T. J. Manuccia, Scanning coherent anti-Stokes Raman microscope, Opt. Lett., 1982, 7, 350–352.

    Article  CAS  PubMed  Google Scholar 

  29. S.-H. Kim, E.-S. Lee, J. Y. Lee, E. S. Lee, B.-S. Lee, J. E. Park and D. W. Moon, Multiplex coherent anti-stokes Raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids, Circ. Res., 2010, 106, 1332–1341.

    Article  CAS  PubMed  Google Scholar 

  30. T. B. Huff, Y. Shi, Y. Fu, H. Wang and J.-X. Cheng, Multimodal Nonlinear Optical Microscopy and Applications to Central Nervous System Imaging, IEEE J. Sel. Top. Quantum Electron., 2008, 14, 4–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, Y. Jia, J. P. Pezacki and A. Stolow, Optimally chirped multimodal CARS microscopy based on a single Ti:sapphire oscillator, Opt. Express, 2009, 17, 2984–2996.

    Article  CAS  PubMed  Google Scholar 

  32. T. Hellerer, A. M. K. Enejder and A. Zumbusch, Spectral focusing: High spectral resolution spectroscopy with broadbandwidth laser pulses, Appl. Phys. Lett., 2004, 85, 25.

    Article  CAS  Google Scholar 

  33. B. G. Saar, L. R. Contreras-Rojas, X. S. Xie and R. H. Guy, Imaging Drug Delivery to Skin with Stimulated Raman Scattering Microscopy, Mol. Pharmaceutics, 2011, 8, 969–975.

    Article  CAS  Google Scholar 

  34. X. Zhang, M. B. J. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom and X. S. Xie, Label-free livecell imaging of nucleic acids using stimulated Raman scattering microscopy, ChemPhysChem, 2012, 13, 1054–1059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie and G. S. Young, Multicolored stain-free histopathology with coherent Raman imaging, Lab. Invest., 2012, 92, 1492–1502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito and J. G. Fujimoto, Optical Coherence Tomography, Science, 1991, 254, 1178–1181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman and J. G. Fujimoto, Ultrahigh-resolution ophthalmic optical coherence tomography, Nat. Med., 2001, 7, 502–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. W. Drexler, H. Sattmann, B. Hermann, T. H. Ko, M. Stur, A. Unterhuber, C. Scholda, O. Findl, M. Wirtitsch, J. G. Fujimoto and A. F. Fercher, Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography, Arch. Ophthalmol., 2003, 121, 695–706.

    Article  PubMed  Google Scholar 

  39. L. Vignali, E. Solinas and E. Emanuele, Research and clinical applications of optical coherence tomography in invasive cardiology: a review, Curr. Cardiol. Rev., 2014, 10, 369–376.

    Article  PubMed  PubMed Central  Google Scholar 

  40. J. Welzel, Optical coherence tomography in dermatology: a review, Skin Res. Technol., 2001, 7, 1–9.

    Article  CAS  PubMed  Google Scholar 

  41. M. Mogensen, L. Thrane, T. M. Jørgensen, P. E. Andersen and G. B. E. Jemec, OCT imaging of skin cancer and other dermatological diseases, J. Biophotonics, 2009, 2, 442–451.

    Article  PubMed  Google Scholar 

  42. R. A. Katkar, S. A. Tadinada, B. T. Amaechi and D. Fried, Optical Coherence Tomography, Dent. Clin. North Am., 2018, 62, 421–434.

    Article  PubMed  Google Scholar 

  43. B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain and B. E. Bouma, Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging, Nat. Med., 2009, 15, 1219–1223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. B. J. Vakoc, D. Fukumura, R. K. Jain and B. E. Bouma, Cancer imaging by optical coherence tomography: preclinical progress and clinical potential, Nat. Rev. Cancer, 2012, 12, 363–368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. C. Kut, K. L. Chaichana, J. Xi, S. M. Raza, X. Ye, E. R. McVeigh, F. J. Rodriguez, A. Quiñones-Hinojosa and X. Li, Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography, Sci. Transl. Med., 2015, 7, 292ra100.

  46. Optical Coherence Tomography: Technology and Applications, ed. W. Drexler and J. G. Fujimoto, Springer International Publishing, 2nd edn, 2015.

  47. M. R. Hee, E. A. Swanson, J. G. Fujimoto and D. Huang, Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging, J. Opt. Soc. Am. B, 1992, 9, 903.

    Article  Google Scholar 

  48. U. Morgner, W. Drexler, F. X. Kärtner, X. D. Li, C. Pitris, E. P. Ippen and J. G. Fujimoto, Spectroscopic optical coherence tomography, Opt. Lett., 2000, 25, 111.

    Article  CAS  PubMed  Google Scholar 

  49. Z. Chen, T. E. Milner, S. Srinivas, X. Wang, A. Malekafzali, M. J. C. van Gemert and J. S. Nelson, Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography, Opt. Lett., 1997, 22, 1119.

    Article  CAS  PubMed  Google Scholar 

  50. H. Tu, Y. Liu, D. Turchinovich, M. Marjanovic, J. K. Lyngsø, J. Lægsgaard, E. J. Chaney, Y. Zhao, S. You, W. L. Wilson, B. Xu, M. Dantus and S. A. Boppart, Stain-free histopathology by programmable supercontinuum pulses, Nat. Photonics, 2016, 10, 534–540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. W. Drexler, M. Liu, A. Kumar, T. Kamali, A. Unterhuber and R. A. Leitgeb, Optical coherence tomography today: speed, contrast, and multimodality, J. Biomed. Opt., 2014, 19, 071412.

    Article  PubMed  Google Scholar 

  52. D. L. Marks and S. A. Boppart, Nonlinear Interferometric Vibrational Imaging, Phys. Rev. Lett., 2004, 92, 123905.

    Article  PubMed  CAS  Google Scholar 

  53. J. S. Bredfeldt, C. Vinegoni, D. L. Marks and S. A. Boppart, Molecularly sensitive optical coherence tomography, Opt. Lett., 2005, 30, 495–497.

    Article  CAS  PubMed  Google Scholar 

  54. C. Vinegoni, J. Bredfeldt, D. Marks and S. Boppart, Nonlinear optical contrast enhancement for optical coherence tomography, Opt. Express, 2004, 12, 331–341.

    Article  PubMed  Google Scholar 

  55. T. Kamali, B. Považay, S. Kumar, Y. Silberberg, B. Hermann, R. Werkmeister, W. Drexler and A. Unterhuber, Hybrid single-source online Fourier transform coherent anti-Stokes Raman scattering/optical coherence tomography, Opt. Lett., 2014, 39, 5709.

    Article  PubMed  Google Scholar 

  56. S. Kumar, T. Kamali, J. M. Levitte, O. Katz, B. Hermann, R. Werkmeister, B. Považay, W. Drexler, A. Unterhuber and Y. Silberberg, Single-pulse CARS based multimodal nonlinear optical microscope for bioimaging, Opt. Express, 2015, 23, 13082.

    Article  CAS  PubMed  Google Scholar 

  57. C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks and S. A. Boppart, Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy, Appl. Phys. Lett., 2006, 88, 053901.

    Article  CAS  Google Scholar 

  58. B. W. Graf and S. A. Boppart, Multimodal In Vivo Skin Imaging with Integrated Optical Coherence and Multiphoton Microscopy, IEEE J. Sel. Top. Quantum Electron., 2012, 18(4), 1280–1286.

  59. E. Beaurepaire, L. Moreaux, F. Amblard and J. Mertz, Combined scanning optical coherence and two-photonexcited fluorescence microscopy, Opt. Lett., 1999, 24, 969–971.

    Article  CAS  PubMed  Google Scholar 

  60. S. Tang, T. B. Krasieva, Z. Chen and B. J. Tromberg, Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source, J. Biomed. Opt., 2006, 11, 020502.

    Article  PubMed  Google Scholar 

  61. S. Yuan, C. A. Roney, J. Wierwille, C.-W. Chen, B. Xu, J. Jiang, H. Ma, A. Cable, R. M. Summers and Y. Chen, Combining Optical Coherence Tomography with Fluorescence Molecular Imaging: Towards Simultaneous Morphology and Molecular Imaging, Phys. Med. Biol., 2010, 55, 191–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. J. Xi, Y. Chen, Y. Zhang, K. Murari, M.-J. Li and X. Li, Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging, Opt. Lett., 2012, 37, 362–364.

    Article  PubMed  PubMed Central  Google Scholar 

  63. S. P. Chong, T. Lai, Y. Zhou and S. Tang, Tri-modal microscopy with multiphoton and optical coherence microscopy/tomography for multi-scale and multi-contrast imaging, Biomed. Opt. Express, 2013, 4, 1584–1594.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Q. Wu, B. E. Applegate and A. T. Yeh, Cornea microstructure and mechanical responses measured with nonlinear optical and optical coherence microscopy using sub-10-fs pulses, Biomed. Opt. Express, 2011, 2, 1135–1146.

    Article  PubMed  PubMed Central  Google Scholar 

  65. S. Yazdanfar, Y. Yu Chen, P. T. C. So and L. H. Laiho, Multifunctional Imaging of Endogenous Contrast by Simultaneous Nonlinear and Optical Coherence Microscopy of Thick Tissues, Microsc. Res. Tech., 2007, 70, 628–633.

    Article  PubMed  Google Scholar 

  66. A. V. Meleshina, O. S. Rogovaya, V. V. Dudenkova, M. A. Sirotkina, M. M. Lukina, A. S. Bystrova, V. G. Krut, D. S. Kuznetsova, E. P. Kalabusheva, A. V. Vasiliev, E. A. Vorotelyak and E. V. Zagaynova, Multimodal label-free imaging of living dermal equivalents including dermal papilla cells, Stem Cell Res. Ther., 2018, 9, 84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart and S. A. Boppart, Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin, J. Biophotonics, 2012, 5(5–6), 437–448.

  68. Y. Jiang, I. Tomov, Y. Wang and Z. Chen, Second-harmonic optical coherence tomography, Opt. Lett., 2004, 29, 1090–1092.

    Article  PubMed  Google Scholar 

  69. B. E. Applegate, C. Yang, A. M. Rollins and J. A. Izatt, Polarization-resolved second-harmonic-generation optical coherence tomography in collagen, Opt. Lett., 2004, 29, 2252–2254.

    Article  PubMed  Google Scholar 

  70. B. W. Graf, Z. Jiang, H. Tu and S. A. Boppart, Dual-spectrum laser source based on fiber continuum generation for integrated optical coherence and multiphoton microscopy, J. Biomed. Opt., 2009, 14, 034019.

    Article  PubMed  CAS  Google Scholar 

  71. B. Jeong, B. Lee, M. S. Jang, H. Nam, S. J. Yoon, T. Wang, J. Doh, B.-G. Yang, M. H. Jang and K. H. Kim, Combined two-photon microscopy and optical coherence tomography using individually optimized sources, Opt. Express, 2011, 19, 13089–13096.

    Article  CAS  PubMed  Google Scholar 

  72. A. T. Yeh, B. Kao, W. G. Jung, Z. Chen, J. S. Nelson and B. J. Tromberg, Imaging wound healing using optical coherence tomography and multiphoton microscopy in an in vitro skin-equivalent tissue model, J. Biomed. Opt., 2004, 9, 248–253.

    Article  PubMed  Google Scholar 

  73. K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner and M. Kaatz, Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases, J. Biophotonics, 2009, 2, 389–397.

    Article  PubMed  Google Scholar 

  74. K. König, Hybrid multiphoton multimodal tomography of in vivo human skin, IntraVital, 2012, 1, 11–26.

    Article  Google Scholar 

  75. A. Alex, J. Weingast, M. Weinigel, M. Kellner-Höfer, R. Nemecek, M. Binder, H. Pehamberger, K. König and W. Drexler, Three-dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology, J. Biophotonics, 2013, 6, 352–362.

    Article  PubMed  Google Scholar 

  76. J. Liu, H. Xie, Z. Yuan, Z. Wang, C. S. D. Lee, W. C. Waltzer and Y. Pan, In vivo bladder imaging with microelectromechanical-systems-based endoscopic spectral domain optical coherence tomography, J. Biomed. Opt., 2007, 12, 034009.

    Article  PubMed  Google Scholar 

  77. C. Dai, X. Liu and S. Jiao, Simultaneous optical coherence tomography and autofluorescence microscopy with a single light source, J. Biomed. Opt., 2012, 17, 080502.

    Article  PubMed  PubMed Central  Google Scholar 

  78. H. Pahlevaninezhad, A. M. D. Lee, G. Hohert, S. Lam, T. Shaipanich, E.-L. Beaudoin, C. MacAulay, C. Boudoux and P. Lane, Endoscopic high-resolution autofluorescence imaging and OCT of pulmonary vascular networks, Opt. Lett., 2016, 41, 3209–3212.

    Article  PubMed  Google Scholar 

  79. J. Mavadia, J. Xi, Y. Chen and X. Li, An all-fiber-optic endoscopy platform for simultaneous OCT and fluorescence imaging, Biomed. Opt. Express, 2012, 3, 2851–2859.

    Article  PubMed  PubMed Central  Google Scholar 

  80. H. Chen, H. Wang, M. N. Slipchenko, Y. K. Jung, Y. Shi, J. Zhu, K. K. Buhman and J. X. Cheng, A multimodal platform for nonlinear optical microscopy and microspectroscopy, Opt. Express, 2009, 17, 1282–1290.

    Article  CAS  PubMed  Google Scholar 

  81. J. Rehbinder, L. Brückner, A. Wipfler, T. Buckup and M. Motzkus, Multimodal nonlinear optical microscopy with shaped 10 fs pulses, Opt. Express, 2014, 22, 28790–28797.

    Article  PubMed  Google Scholar 

  82. D. Li, W. Zheng, Y. Zeng and J. Y. Qu, In vivo and simultaneous multimodal imaging: Integrated multiplex coherent anti-Stokes Raman scattering and two-photon microscopy, Appl. Phys. Lett., 2010, 97, 223702.

    Article  CAS  Google Scholar 

  83. W. Langbein, Israel Rocha-Mendoza and Paola Borri, Coherent anti-Stokes Raman micro-spectroscopy using spectral focusing: theory and experiment, J. Raman Spectrosc., 2009, 40, 800–808.

    Article  CAS  Google Scholar 

  84. P. W. Roth, A. J. Maclean, D. Burns and A. J. Kemp, Direct diode-laser pumping of a mode-locked Ti:sapphire laser, Opt. Lett., 2011, 36, 304.

    Article  CAS  PubMed  Google Scholar 

  85. R. Sawada, H. Tanaka, N. Sugiyama and F. Kannari, Wavelength-multiplexed pumping with 478- and 520-nm indium gallium nitride laser diodes for Ti:sapphire laser, Appl. Opt., 2017, 56, 1654.

    Article  CAS  PubMed  Google Scholar 

  86. M. Andreana, T. Le, A. K. Hansen, A. J. Verhoef, O. B. Jensen, P. E. Andersen, P. Slezak, W. Drexler, A. Fernández and A. Unterhuber, Epi-detecting label-free multimodal imaging platform using a compact diode-pumped femtosecond solidstate laser, J. Biomed. Opt., 2017, 22, 1.

    Article  Google Scholar 

  87. K. König, P. Andersen, T. Le and H. G. Breunig, Multiphoton imaging with a novel compact diode-pumped Ti:sapphire oscillator, Microsc. Res. Tech., 2015, 78, 1154–1158.

    Article  PubMed  Google Scholar 

  88. A. Unterhuber, B. Považay, A. Müller, O. B. Jensen, M. Duelk, T. Le, P. M. Petersen, C. Velez, M. Esmaeelpour, P. E. Andersen and W. Drexler, Simultaneous dual wavelength eye-tracked ultrahigh resolution retinal and choroidal optical coherence tomography, Opt. Lett., 2013, 38, 4312.

    Article  CAS  PubMed  Google Scholar 

  89. A. Unterhuber, B. Považay, B. Hermann, H. Sattmann, W. Drexler, V. Yakovlev, G. Tempea, C. Schubert, E. M. Anger and P. K. Ahnelt, Compact, low-cost Ti: Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography, Opt. Lett., 2003, 28, 905–907.

    Article  CAS  PubMed  Google Scholar 

  90. T. A. Pologruto, B. L. Sabatini and K. Svoboda, ScanImage: flexible software for operating laser scanning microscopes, Biomed. Eng. Online, 2003, 2, 13.

    Article  PubMed  PubMed Central  Google Scholar 

  91. R. Nejati, C. Skobowiat and A. T. Slominski, Commentary on the practical guide for the study of sebaceous glands, Exp. Dermatol., 2013, 22, 629–630.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Y. Jung, J. Tam, H. Ray Jalian, R. Rox Anderson and C. L. Evans, Longitudinal, 3D In Vivo Imaging of Sebaceous Glands by Coherent Anti-Stokes Raman Scattering Microscopy: Normal Function and Response to Cryotherapy, J. Invest. Dermatol., 2015, 135, 39–44.

    Article  PubMed  Google Scholar 

  93. M. Manfredini, M. Greco, F. Farnetani, S. Ciardo, N. De Carvalho, V. D. Mandel, M. Starace and G. Pellacani, Acne: morphologic and vascular study of lesions and surrounding skin by means of optical coherence tomography, J. Eur. Acad. Dermatol. Venereol., 2017, 31, 1541–1546.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Marco Andreana, Ryan Sentosa, Mikael T. Erkkilä, Wolfgang Drexler & Angelika Unterhuber

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  1. Marco Andreana
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  2. Ryan Sentosa
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  3. Mikael T. Erkkilä
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  4. Wolfgang Drexler
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  5. Angelika Unterhuber
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Corresponding author

Correspondence to Angelika Unterhuber.

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Andreana, M., Sentosa, R., Erkkilä, M.T. et al. Depth resolved label-free multimodal optical imaging platform to study morpho-molecular composition of tissue. Photochem Photobiol Sci 18, 997–1008 (2019). https://doi.org/10.1039/c8pp00410b

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  • Received: 18 September 2018

  • Accepted: 08 January 2019

  • Published: 27 October 2020

  • Issue Date: May 2019

  • DOI: https://doi.org/10.1039/c8pp00410b

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