Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy.

Journal: Nature biomedical engineering
PMID:

Abstract

Obtaining frozen sections of bone tissue for intraoperative examination is challenging. To identify the bony edge of resection, orthopaedic oncologists therefore rely on pre-operative X-ray computed tomography or magnetic resonance imaging. However, these techniques do not allow for accurate diagnosis or for intraoperative confirmation of the tumour margins, and in bony sarcomas, they can lead to bone margins up to 10-fold wider (1,000-fold volumetrically) than necessary. Here, we show that real-time three-dimensional contour-scanning of tissue via ultraviolet photoacoustic microscopy in reflection mode can be used to intraoperatively evaluate undecalcified and decalcified thick bone specimens, without the need for tissue sectioning. We validate the technique with gold-standard haematoxylin-and-eosin histology images acquired via a traditional optical microscope, and also show that an unsupervised generative adversarial network can virtually stain the ultraviolet-photoacoustic-microscopy images, allowing pathologists to readily identify cancerous features. Label-free and slide-free histology via ultraviolet photoacoustic microscopy may allow for rapid diagnoses of bone-tissue pathologies and aid the intraoperative determination of tumour margins.

Authors

  • Rui Cao
    Department of Cardiology of Lu'an People's Hospital, Lu'an Hospital of Anhui Medical University, Lu'an, China.
  • Scott D Nelson
    George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA; University of Utah, Salt Lake City, UT, USA.
  • Samuel Davis
    Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Yu Liang
    School of Software, Beijing Institute of Technology, Beijing 100081, China.
  • Yilin Luo
    Department of Medical Imaging, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
  • Yide Zhang
    Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Brooke Crawford
    UCLA Medical Center, Los Angeles, CA, 90095, USA.
  • Lihong V Wang
    Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA. lvw@caltech.edu.