Skip to main content

Recent advances toward clinical applications of photoacoustic microscopy: a review

Science China Life Sciences volume 63, pages 1798–1812 (2020)Cite this article

Abstract

Photoacoustic imaging (PAI) is an emerging technology that has been dramatically developed in the last decade. PAI, a combination of optical illumination and ultrasound detection, allows us to achieve fine resolution and obtain fruitful information of endogenous and exogenous chromophores. Among PAI imaging techniques, photoacoustic computed tomography (PACT) has been extensively used in human studies due to its deep tissue penetration (several centimeters). Alternatively, photoacoustic microscopy (PAM) offers higher resolution at the expense of penetration depth, which can also be advantageous in clinics. Recently, there has been increasing attention and studies on PAM of human tissues. In this paper, we will review principles of PAM and its applications to human tissues, including the breast tissue, carotid atheroma tissue, eye, gastrointestinal tissue, ovarian tissue and tooth ex vivo as well as the oral cavity and dermatological tissue in vivo. The paper is closed with the outlook regarding the potential applications of PAM in clinics.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Baik, J.W., Kim, J.Y., Cho, S., Choi, S., Kim, J., and Kim, C. (2019). Super wide-field photoacoustic microscopy of animals and humans in vivo. IEEE Trans Med Imag 1.

    Google Scholar 

  • Bitton, R., Zemp, R., Yen, J., Wang, L.V., and Shung, K.K. (2009). A 3-D high-frequency array based 16 channel photoacoustic microscopy system for in vivo micro-vascular imaging. IEEE Trans Med Imag 28, 1190–1197.

    Google Scholar 

  • Bungart, B.L., Lan, L., Wang, P., Li, R., Koch, M.O., Cheng, L., Masterson, T.A., Dundar, M., and Cheng, J.X. (2018). Photoacoustic tomography of intact human prostates and vascular texture analysis identify prostate cancer biopsy targets. Photoacoustics 11, 46–55.

    PubMed  PubMed Central  Google Scholar 

  • Chen, Q., Guo, H., Jin, T., Qi, W., Xie, H., and Xi, L. (2018). Ultracompact high-resolution photoacoustic microscopy. Opt Lett 43, 1615.

    PubMed  Google Scholar 

  • Chen, Q., Guo, H., Qi, W., Gan, Q., Yang, L., Ke, B., Chen, X., Jin, T., and Xi, L. (2019). Assessing hemorrhagic shock: Feasibility of using an ultracompact photoacoustic microscope. J Biophotonics 12, e201800348.

    PubMed  Google Scholar 

  • Chen, Z., Rank, E., Meiburger, K.M., Sinz, C., Hodul, A., Zhang, E., Hoover, E., Minneman, M., Ensher, J., Beard, P.C., et al. (2017). Noninvasive multimodal optical coherence and photoacoustic tomography for human skin imaging. Sci Rep 7, 17975.

    PubMed  PubMed Central  Google Scholar 

  • Cheng, Z., Ma, H., Wang, Z., and Yang, S. (2018). 3D depth-coded photoacoustic microscopy with a large field of view for human skin imaging. Chin Opt Lett 16, 081701.

    Google Scholar 

  • Choi, W., Park, E.Y., Jeon, S., and Kim, C. (2018). Clinical photoacoustic imaging platforms. Biomed Eng Lett 8, 139–155.

    PubMed  PubMed Central  Google Scholar 

  • Dadkhah, A., Zhou, J., Yeasmin, N., and Jiao, S. (2019). Integrated multimodal photoacoustic microscopy with OCT-guided dynamic focusing. Biomed Opt Express 10, 137.

    CAS  PubMed  Google Scholar 

  • Deng, Z., and Li, C. (2016). Noninvasively measuring oxygen saturation of human finger-joint vessels by multi-transducer functional photoacoustic tomography. J Biomed Opt 21, 061009.

    Google Scholar 

  • Favazza, C.P., Cornelius, L.A., and Wang, L.V. (2011a). In vivo functional photoacoustic microscopy of cutaneous microvasculature in human skin. J Biomed Opt 16, 026004.

    PubMed  PubMed Central  Google Scholar 

  • Favazza, C.P., Hu, S., Huang, V., Jassim, O., Cornelius, L.A., and Wang, L. V. (2011b). In vivo multiscale photoacoustic microscopy of human skin. In Photons Plus Ultrasound: Imaging and Sensing, 2011. pp. 789946.

    Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Guney, G., Uluc, N., Demirkiran, A., Aytac-Kipergil, E., Unlu, M.B., and Birgul, O. (2019). Comparison of noise reduction methods in photoacoustic microscopy. Comput Biol Med 109, 333–341.

    PubMed  Google Scholar 

  • Hsu, H.C., Wang, L., and Wang, L.V. (2016). In vivo photoacoustic microscopy of human cuticle microvasculature with single-cell resolution. J Biomed Opt 21, 056004.

    PubMed Central  Google Scholar 

  • Hu, S., and Wang, L.V. (2013). Optical-resolution photoacoustic microscopy: Auscultation of biological systems at the cellular level. Biophys J 105, 841–847.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes, D.A., Sampathkumar, A., Longbottom, C., and Kirk, K.J. (2015). Imaging and detection of early stage dental caries with an all-optical photoacoustic microscope. J Phys Conf Ser 581, 012002.

    Google Scholar 

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

    PubMed  Google Scholar 

  • Jin, T., Guo, H., Jiang, H., Ke, B., and Xi, L. (2017). Portable optical resolution photoacoustic microscopy (pORPAM) for human oral imaging. Opt Lett 42, 4434.

    PubMed  Google Scholar 

  • Jin, T., Guo, H., Yao, L., Xie, H., Jiang, H., and Xi, L. (2018). Portable optical-resolution photoacoustic microscopy for volumetric imaging of multiscale organisms. J Biophotonics 11, e201700250.

    PubMed  Google Scholar 

  • Jnawali, K., Chinni, B., Dogra, V., and Rao, N. (2019a). Transfer learning for automatic cancer tissue detection using multispectral photoacoustic imaging. In Medical Imaging 2019 Computer-Aided Diagnosis, pp. 140.

    Google Scholar 

  • Jnawali, K., Chinni, B., Dogra, V., Sinha, S., Rao, N. (2019b). Deep 3D convolutional neural network for automatic cancer tissue detection using multispectral photoacoustic imaging. In Medical Imaging 2019 Ultrason Imaging Tomogr, pp. 51.

    Google Scholar 

  • Jo, J., Tian, C., Xu, G., Sarazin, J., Schiopu, E., Gandikota, G., and Wang, X. (2018). Photoacoustic tomography for human musculoskeletal imaging and inflammatory arthritis detection. Photoacoustics 12, 82–89.

    PubMed  PubMed Central  Google Scholar 

  • Kosik, I., Brackstone, M., Kornecki, A., Chamson-Reig, A., Wong, P., Araghi, M.H., and Carson, J.J.L. (2019). Intraoperative photoacoustic screening of breast cancer: a new perspective on malignancy visualization and surgical guidance. J Biomed Opt 24, 1.

    PubMed  Google Scholar 

  • Lei, H., Johnson, L.A., Liu, S., Moons, D.S., Ma, T., Zhou, Q., Rice, M.D., Ni, J., Wang, X., Higgins, P.D.R., et al. (2016). Characterizing intestinal inflammation and fibrosis in Crohn’s disease by photoacoustic imaging: feasibility study. Biomed Opt Express 7, 2837.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leng, X., Chapman, W., Rao, B., Nandy, S., Chen, R., Rais, R., Gonzalez, I., Zhou, Q., Chatterjee, D., Mutch, M., et al. (2018). Feasibility of coregistered ultrasound and acoustic-resolution photoacoustic imaging of human colorectal cancer. Biomed Opt Express 9, 5159.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Lin, R., Liu, C., Chen, J., Liu, H., Zheng, R., Gong, X., and Song, L. (2018). In vivo photoacoustic/ultrasonic dual-modality endoscopy with a miniaturized full field-of-view catheter. J Biophotonics 11, e201800034.

    PubMed  Google Scholar 

  • Li, Y., Lu, G., Chen, J.J., Jing, J.C., Huo, T., Chen, R., Jiang, L., Zhou, Q., and Chen, Z. (2019). PMN-PT/Epoxy 1-3 composite based ultrasonic transducer for dual-modality photoacoustic and ultrasound endoscopy. Photoacoustics 15, 100138.

    PubMed  PubMed Central  Google Scholar 

  • Lin, L., Zhang, P., Xu, S., Shi, J., Li, L., Yao, J., Wang, L., Zou, J., and Wang, L.V. (2017). Handheld optical-resolution photoacoustic microscopy. J Biomed Opt 22, 041002.

    Google Scholar 

  • Liu, W., and Yao, J. (2018). Photoacoustic microscopy: principles and biomedical applications. Biomed Eng Lett 8, 203–213.

    PubMed  PubMed Central  Google Scholar 

  • Ma, H., Cheng, Z., Wang, Z., Xiong, K., and Yang, S. (2019). Fast controllable confocal focus photoacoustic microscopy using a synchronous zoom opto-sono objective. Opt Lett 44, 1880.

    CAS  PubMed  Google Scholar 

  • McNally, L.R., Mezera, M., Morgan, D.E., Frederick, P.J., Yang, E.S., Eltoum, I.E., and Grizzle, W.E. (2016). Current and emerging clinical applications of multispectral optoacoustic tomography (MSOT) in oncology. Clin Cancer Res 22, 3432–3439.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Menke, J. (2015). Photoacoustic breast tomography prototypes with reported human applications. Eur Radiol 25, 2205–2213.

    PubMed  Google Scholar 

  • Nie, L., Cai, X., Maslov, K., Garcia-Uribe, A., Anastasio, M.A., and Wang, L.V. (2012). Photoacoustic tomography through a whole adult human skull with a photon recycler. J Biomed Opt 17, 110506.

    PubMed  PubMed Central  Google Scholar 

  • Omar, M., Aguirre, J., and Ntziachristos, V. (2019). Optoacoustic mesoscopy for biomedicine. Nat Biomed Eng 3, 354–370.

    CAS  PubMed  Google Scholar 

  • Park, K., Kim, J.Y., Lee, C., Jeon, S., Lim, G., and Kim, C. (2017). Handheld photoacoustic microscopy probe. Sci Rep 7, 13359.

    PubMed  PubMed Central  Google Scholar 

  • Park, S., Lee, C., Kim, J., and Kim, C. (2014). Acoustic resolution photoacoustic microscopy. Biomed Eng Lett 4, 213–222.

    Google Scholar 

  • Periyasamy, V., Das, N., Sharma, A., and Pramanik, M. (2019). 1064 nm acoustic resolution photoacoustic microscopy. J Biophotonics 12, https://doi.org/10.1002/jbio.201800357.

  • Periyasamy, V., Rangaraj, M., and Pramanik, M. (2018). Photoacoustic imaging of teeth for dentine imaging and enamel characterization. In Lasers Dent XXIV, pp. 8.

    Google Scholar 

  • Prahl, S. (1998). Tabulated molar extinction coefficient for hemoglobin in water. https://omlc.org/spectra/hemoglobin/summary.html.

    Google Scholar 

  • Qi, W., Chen, Q., Guo, H., Xie, H., and Xi, L. (2018). Miniaturized optical resolution photoacoustic microscope based on a microelectromechanical systems scanning mirror. Micromachines 9, 288.

    PubMed Central  Google Scholar 

  • Qin, W., Chen, Q., and Xi, L. (2018). A handheld microscope integrating photoacoustic microscopy and optical coherence tomography. Biomed Opt Express 9, 2205.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qin, W., Qi, W., Jin, T., Guo, H., and Xi, L. (2017). In vivo oral imaging with integrated portable photoacoustic microscopy and optical coherence tomography. Appl Phys Lett 111, 263704.

    Google Scholar 

  • Qu, Y., Li, C., Shi, J., Chen, R., Xu, S., Rafsanjani, H., Maslov, K., Krigman, H., Garvey, L., Hu, P., et al. (2018). Transvaginal fast-scanning optical-resolution photoacoustic endoscopy. J Biomed Opt 23, 1.

    CAS  PubMed  Google Scholar 

  • Rao, B., Cai, X., Favazza, C., Yao, J., Li, L., Duong, S., Liaw, L.H., Holzman, J., Wilder-Smith, P., and Wang, L.V. (2011). Photoacoustic microscopy of human teeth. In Lasers Dent XVII, 78840.

    Google Scholar 

  • Saijo, Y., Ida, T., Iwazaki, H., Shintate, R., Sato, K., Hiratsuka, T., Yoshizawa, S., and Umemura, S. (2019). Visualization of skin morphology and microcirculation with high frequency ultrasound and dual-wavelength photoacoustic microscope. In Photons Plus Ultrasound: Imaging and Sensing, 2019. pp. 120.

    Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Shu, X., Li, H., Dong, B., Sun, C., and Zhang, H.F. (2017). Quantifying melanin concentration in retinal pigment epithelium using broadband photoacoustic microscopy. Biomed Opt Express 8, 2851.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Song, L., Maslov, K., Shung, K.K., and Wang, L.V. (2010). Ultrasoundarray-based real-time photoacoustic microscopy of human pulsatile dynamics in vivo. J Biomed Opt 15, 021303.

    PubMed  PubMed Central  Google Scholar 

  • Strohm, E.M., Moore, M.J., and Kolios, M.C. (2016). Single cell photoacoustic microscopy: a review. IEEE J Sel Top Quantum Electron 22, 137–151.

    Google Scholar 

  • Subochev, P., Orlova, A., Smolina, E., Kirillov, A., Shakhova, N., and Turchin, I. (2018). Raster-scan optoacoustic angiography reveals 3D microcirculatory changes during cuffed occlusion. Laser Phys Lett 15, 045602.

    Google Scholar 

  • Upputuri, P.K., and Pramanik, M. (2017). Recent advances toward preclinical and clinical translation of photoacoustic tomography: a review. J Biomed Opt 22, 041006.

    Google Scholar 

  • Valluru, K.S., and Willmann, J.K. (2016). Clinical photoacoustic imaging of cancer. Ultrasonography 35, 267–280.

    PubMed  PubMed Central  Google Scholar 

  • Wang, T., Yang, Y., Alqasemi, U., Kumavor, P.D., Wang, X., Sanders, M., Brewer, M., and Zhu, Q. (2013). Characterization of ovarian tissue based on quantitative analysis of photoacoustic microscopy images. Biomed Opt Express 4, 2763.

    PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Wang, D., Hubbell, R., and Xia, J. (2017). Second generation slit-based photoacoustic tomography system for vascular imaging in human. J Biophotonics 10, 799–804.

    CAS  PubMed  Google Scholar 

  • Wong, T.T.W., Zhang, R., Hai, P., Zhang, C., Pleitez, M.A., Aft, R.L., Novack, D.V., and Wang, L.V. (2017). Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy. Sci Adv 3, e1602168.

    PubMed  PubMed Central  Google Scholar 

  • Wu, M., Springeling, G., Lovrak, M., Mastik, F., Iskander-Rizk, S., Wang, T., van Beusekom, H.M.M., van der Steen, A.F.W., and Van Soest, G. (2017). Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second. Biomed Opt Express 8, 943.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, J.M., Chen, R., Favazza, C., Yao, J., Li, C., Hu, Z., Zhou, Q., Shung, K.K., and Wang, L.V. (2012a). A 25-mm diameter probe for photoacoustic and ultrasonic endoscopy. Opt Express 20, 23944.

    PubMed  PubMed Central  Google Scholar 

  • Yang, J.M., Favazza, C., Chen, R., Yao, J., Cai, X., Maslov, K., Zhou, Q., Shung, K.K., and Wang, L.V. (2012b). Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat Med 18, 1297–1302.

    CAS  PubMed  Google Scholar 

  • Yang, J.M., Li, C., Chen, R., Zhou, Q., Shung, K.K., and Wang, L.V. (2014). Catheter-based photoacoustic endoscope. J Biomed Opt 19, 066001.

    PubMed  PubMed Central  Google Scholar 

  • Yao, J., and Wang, L.V. (2014). Sensitivity of photoacoustic microscopy. Photoacoustics 2, 87–101.

    PubMed  PubMed Central  Google Scholar 

  • Yao, Q., Ding, Y., Liu, G., and Zeng, L. (2017). Low-cost photoacoustic imaging systems based on laser diode and light-emitting diode excitation. J Innov Opt Health Sci 10, 1730003.

    CAS  Google Scholar 

  • Yoon, T.J., and Cho, Y.S. (2013). Recent advances in photoacoustic endoscopy. World J Gastrointest Endosc 5, 534.

    PubMed  PubMed Central  Google Scholar 

  • Zafar, H., Leahy, M., Wijns, W., Kolios, M., Zafar, J., Johnson, N., and Sharif, F. (2018). Photoacoustic cardiovascular imaging: a new technique for imaging of atherosclerosis and vulnerable plaque detection. Biomed Phys Eng Express 4, 032002.

    Google Scholar 

  • Zhang, H.F., Maslov, K., Li, M.L., Stoica, G., and Wang, L.V. (2006a). In vivo volumetric imaging of subcutaneous microvasculature by photoacoustic microscopy. Opt Express 14, 9317–9323.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Zhang, J., Chen, B., Zhou, M., Lan, H., and Gao, F. (2019). photoacoustic image classification and segmentation of breast cancer: a feasibility study. IEEE Access 7, 5457–5466.

    Google Scholar 

  • Zhang, X., Ding, Q., Qian, X., Tao, C., and Liu, X. (2018). Reflectionmode optical-resolution photoacoustic microscopy with high detection sensitivity by using a perforated acoustic mirror. Appl Phys Lett 113, 183706.

    Google Scholar 

  • Zhao, T., Desjardins, A.E., Ourselin, S., Vercauteren, T., and Xia, W. (2019). Minimally invasive photoacoustic imaging: current status and future perspectives. Photoacoustics 16, 100146.

    PubMed  PubMed Central  Google Scholar 

  • Zhou, Y., Yi, X., Xing, W., Hu, S., Maslov, K.I., and Wang, L.V. (2014). Microcirculatory changes identified by photoacoustic microscopy in patients with complex regional pain syndrome type I after stellate ganglion blocks. J Biomed Opt 19, 086017.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (61775134).

Author information

Affiliations

  1. University of Michigan-Shanghai Jiao Tong University Joint Institute, Shanghai Jiao Tong University, Shanghai, 200240, China

    Myeongsu Seong & Sung-Liang Chen

  2. State Key Laboratory of Advanced Optical Communication Systems and Networks, Shanghai Jiao Tong University, Shanghai, 200240, China

    Sung-Liang Chen

Authors
  1. Myeongsu Seong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung-Liang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Liang Chen.

Ethics declarations

Compliance and ethics The author(s) declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Seong, M., Chen, SL. Recent advances toward clinical applications of photoacoustic microscopy: a review. Sci. China Life Sci. 63, 1798–1812 (2020). https://doi.org/10.1007/s11427-019-1628-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-019-1628-7

Keywords

  • photoacoustic imaging
  • photoacoustic microscopy
  • clinical application
  • human tissue
  • in vivo