Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis

Cell Rep Med. 2020 May 19;1(2):100017. doi: 10.1016/j.xcrm.2020.100017.

Abstract

While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling sensitive assessments of the redox ratio and mitochondrial fragmentation, which yield metrics of metabolic function and heterogeneity. Simultaneous characterization of morphological features, such as the depth-dependent variation of the nuclear:cytoplasmic ratio, is demonstrated. Multi-parametric analysis combining several metabolic metrics with morphological ones enhances significantly the diagnostic accuracy of identifying high-grade squamous intraepithelial lesions. Our results motivate the translation of such functional metabolic imaging to in vivo studies, which may enable improved identification of cervical lesions, and other precancers, at the bedside.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cervix Uteri / diagnostic imaging*
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Epithelium / diagnostic imaging
  • Epithelium / metabolism
  • Epithelium / pathology
  • Female
  • Flavin-Adenine Dinucleotide / metabolism
  • Humans
  • Metabolic Networks and Pathways
  • Mitochondrial Dynamics / physiology
  • NAD / metabolism
  • NADP / metabolism
  • Optical Imaging / methods*
  • Precancerous Conditions / diagnosis*
  • Precancerous Conditions / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Staining and Labeling
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Neoplasms / diagnosis*

Substances

  • NAD
  • Flavin-Adenine Dinucleotide
  • NADP