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Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy

Abstract

Imaging plays a critical role in the diagnosis and assessment of dermatological conditions. However, optical or optoacoustic microscopy techniques are limited to visualizing superficial skin features owing to strong photon scattering, whereas ultrasound methods, which can probe deeper-seated tissue, lack the contrast to image pathophysiological mechanisms in detail. Here, we demonstrate that raster-scan optoacoustic mesoscopy (RSOM) implemented in ultra-broadband (10–180 MHz) detection mode bridges the depth capabilities of ultrasound and the resolution range and high contrast of optical methods in clinical dermatology. Using tomographic reconstruction and frequency equalization to represent low and high spatial-frequency components, we visualize skin morphology and vascular patterns in the dermis and sub-dermis of psoriasis patients, enabling quantification of inflammation and other biomarkers of psoriasis without the need for contrast agents. Implemented in a handheld device, we showcase how label-free biomarkers detected by RSOM correlate with clinical score. The method can also be extended to assess a larger spectrum of dermatological conditions.

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Figure 1: Skin imaging with the portable UB-RSOM system, using colour coding of frequency bands.
Figure 2: UB-RSOM of healthy skin versus adjacent psoriatic skin and validation by histology.
Figure 3: Clinical relevance of UB-RSOM measurements.

References

  1. Nestle, F. O., Kaplan, D. H. & Barker, J. Psoriasis. N. Engl. J. Med. 361, 496–509 (2009).

    Article  CAS  Google Scholar 

  2. Horn, E. J. et al. Association of patient-reported psoriasis severity with income and employment. J. Am. Acad. Dermatol. 57, 963–971 (2007).

    Article  Google Scholar 

  3. Boehncke, W. H. & Schon, M. P. Psoriasis. Lancet 386, 983–994 (2015).

    Article  CAS  Google Scholar 

  4. Griffiths, C. E. & Barker, J. N. Pathogenesis and clinical features of psoriasis. Lancet 370, 263–271 (2007).

    Article  CAS  Google Scholar 

  5. Oji, V. & Luger, T. A. The skin in psoriasis: assessment and challenges. Clin. Exp. Rheumatol. 33, S14–S19 (2015).

    PubMed  Google Scholar 

  6. Ashcroft, D. M., Wan Po, A. L., Williams, H. C. & Griffiths, C. E. Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality. Br. J. Dermatol. 141, 185–191 (1999).

    Article  CAS  Google Scholar 

  7. Marks, R. Measurement of the response to treatment in psoriasis. J. Dermatolog. Treat. 7, S7–S10 (1996).

    Google Scholar 

  8. Ryan, C. et al. Research gaps in psoriasis: opportunities for future studies. J. Am. Acad. Dermatol. 70, 146–167 (2014).

    Article  Google Scholar 

  9. Lacarrubba, F., Pellacani, G., Gurgone, S., Verzi, A. E. & Micali, G. Advances in non-invasive techniques as aids to the diagnosis and monitoring of therapeutic response in plaque psoriasis: a review. Int. J. Dermatol. 54, 626–634 (2015).

    Article  Google Scholar 

  10. Archid, R. et al. Confocal laser-scanning microscopy of capillaries in normal and psoriatic skin. J. Biomed. Opt. 17, 101511 (2012).

    Article  Google Scholar 

  11. Alex, A. et al. Multispectral in vivo three-dimensional optical coherence tomography of human skin. J. Biomed. Opt. 15, 026025 (2010).

    Article  Google Scholar 

  12. Pan, Y. & Farkas, D. L. Noninvasive imaging of living human skin with dual-wavelength optical coherence tomography in two and three dimensions. J. Biomed. Opt. 3, 446–455 (1998).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  14. Blatter, C. et al. In situ structural and microangiographic assessment of human skin lesions with high-speed OCT. Biomed. Opt. Express 3, 2636–2646 (2012).

    Article  Google Scholar 

  15. Qin, J., Jiang, J., An, L., Gareau, D. & Wang, R. K. In vivo volumetric imaging of microcirculation within human skin under psoriatic conditions using optical microangiography. Lasers Surg. Med. 43, 122–129 (2011).

    Article  Google Scholar 

  16. Errico, C. et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature 527, 499–502 (2015).

    Article  CAS  Google Scholar 

  17. Gutierrez, M. et al. High-frequency sonography in the evaluation of psoriasis: nail and skin involvement. J. Ultrasound. Med. 28, 1569–1574 (2009).

    Article  Google Scholar 

  18. Jetzfellner, T. et al. Optoacoustic tomography with varying illumination and non-uniform detection patterns. J. Opt. Soc. Am. 27, 2488–2495 (2010).

    Article  Google Scholar 

  19. Mancardi, D., Varetto, G., Bucci, E., Maniero, F. & Guiot, C. Fractal parameters and vascular networks: facts and artifacts. Theor. Biol. Med. Model. 5, 12 (2008).

    Article  Google Scholar 

  20. Favazza, C. P., Jassim, O., Cornelius, L. A. & Wang, L. V. In vivo photoacoustic microscopy of human cutaneous microvasculature and a nevus. J. Biomed. Opt. 16, 016015 (2011).

    Article  Google Scholar 

  21. Braverman, I. M. & Keh-Yen, A. Ultrastructure of the human dermal microcirculation. III. The vessels in the mid- and lower dermis and subcutaneous fat. J. Invest. Dermatol. 77, 297–304 (1981).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  23. Schwarz, M., Omar, M., Buehler, A., Aguirre, J. & Ntziachristos, V. Implications of ultrasound frequency in optoacoustic mesoscopy of the skin. IEEE Trans. Med. Imaging 34, 672–677 (2014).

    Article  Google Scholar 

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

    Article  Google Scholar 

  25. 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).

    Article  Google Scholar 

  26. Verstege, A. et al. The predictive value of the skin prick test weal size for the outcome of oral food challenges. Clin. Exp. Allergy 35, 1220–1226 (2005).

    Article  CAS  Google Scholar 

  27. Schwarz, M., Buehler, A., Aguirre, J. & Ntziachristos, V. Three-dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin in vivo . J. Biophotonics 9, 55–60 (2015).

    Article  Google Scholar 

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

    Article  Google Scholar 

  29. Turner, J., Estrada, H., Kneipp, M. & Razansky, D. Improved optoacoustic microscopy through three-dimensional spatial impulse response synthetic aperture focusing technique. Opt. Lett. 39, 3390–3393 (2014).

    Article  Google Scholar 

  30. Foroutan-pour, K., Dutilleul, P. & Smith, D. L. Advances in the implementation of the box-counting method of fractal dimension estimation. Appl. Math. Comput. 105, 15 (1999).

    Google Scholar 

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Acknowledgements

We acknowledge funding from European Grant INNODERM (687866) Horizon 2020 and Deutsche Forschungsgemeinschaft, Germany (Leibniz Prize 2013; NT 3/10-1).

Author information

Authors and Affiliations

Authors

Contributions

J.A. designed and developed the imaging system, designed and performed the experiments, processed the data, provided conceptual input and wrote the paper. M.S. developed the imaging system, performed the experiments, processed the data. N.G. provided conceptual input and performed the histology experiments. M.O. developed the imaging system and performed the characterization experiments. A.B. provided conceptual input. K.E. provided conceptual input and designed the experiments. V.N. provided conceptual input, designed the experiments, supervised and led the research, and wrote the paper. J.A., M.S., M.O., A.B. and V.N. revised the text after the referees’ comments.

Corresponding author

Correspondence to Vasilis Ntziachristos.

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Competing interests

V.N. is a shareholder in iThera-Medical GmbH, Munich, Germany.

Supplementary information

Supplementary Information

Supplementary notes and figures. (PDF 1061 kb)

Supplementary Video 1

Three-dimensional skin visualization of healthy skin by ultra-broadband raster scan optoacoustic mesoscopy. (AVI 2196 kb)

Supplementary Video 2

Three-dimensional skin visualization of psoriatic skin by ultra-broadband raster scan optoacoustic mesoscopy. (AVI 3417 kb)

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Aguirre, J., Schwarz, M., Garzorz, N. et al. Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy. Nat Biomed Eng 1, 0068 (2017). https://doi.org/10.1038/s41551-017-0068

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