Deep learning-enabled realistic virtual histology with ultraviolet photoacoustic remote sensing microscopy

Nat Commun. 2023 Sep 25;14(1):5967. doi: 10.1038/s41467-023-41574-2.

Abstract

The goal of oncologic surgeries is complete tumor resection, yet positive margins are frequently found postoperatively using gold standard H&E-stained histology methods. Frozen section analysis is sometimes performed for rapid intraoperative margin evaluation, albeit with known inaccuracies. Here, we introduce a label-free histological imaging method based on an ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent generative adversarial network for realistic virtual staining. Unstained tissues are scanned at rates of up to 7 mins/cm2, at resolution equivalent to 400x digital histopathology. Quantitative validation suggests strong concordance with conventional histology in benign and malignant prostate and breast tissues. In diagnostic utility studies we demonstrate a mean sensitivity and specificity of 0.96 and 0.91 in breast specimens, and respectively 0.87 and 0.94 in prostate specimens. We also find virtual stain quality is preferred (P = 0.03) compared to frozen section analysis in a blinded survey of pathologists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coloring Agents
  • Deep Learning*
  • Humans
  • Male
  • Microscopy*
  • Remote Sensing Technology
  • Spectrum Analysis

Substances

  • Coloring Agents

Grants and funding