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Non-invasive scoring of cellular atypia in keratinocyte cancers in 3D LC-OCT images using Deep Learning

Authors
  • Fischman, Sébastien1
  • Pérez-Anker, Javiera2, 3
  • Tognetti, Linda4
  • Di Naro, Angelo4
  • Suppa, Mariano5, 6, 7
  • Cinotti, Elisa4, 6
  • Viel, Théo1
  • Monnier, Jilliana6, 8
  • Rubegni, Pietro4
  • del Marmol, Véronique5
  • Malvehy, Josep2, 3
  • Puig, Susana2, 3
  • Dubois, Arnaud9
  • Perrot, Jean-Luc10
  • 1 DAMAE Medical, Paris, France , Paris (France)
  • 2 University of Barcelona, Barcelona, Spain , Barcelona (Spain)
  • 3 CIBER de enfermedades raras, Instituto de Salud Carlos III, Barcelona, Spain , Barcelona (Spain)
  • 4 University of Siena, Siena, Italy , Siena (Italy)
  • 5 Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium , Brussels (Belgium)
  • 6 Groupe d’Imagerie Cutanée Non Invasive (GICNI) of the Société Française de Dermatologie (SFD), Paris, France , Paris (France)
  • 7 Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium , Brussels (Belgium)
  • 8 la Timone hospital, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France , Marseille (France)
  • 9 Laboratoire Charles Fabry, Palaiseau, France , Palaiseau (France)
  • 10 University Hospital of Saint-Etienne, Saint-Etienne, France , Saint-Etienne (France)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Jan 10, 2022
Volume
12
Issue
1
Identifiers
DOI: 10.1038/s41598-021-04395-1
Source
Springer Nature
Disciplines
  • article
License
Green

Abstract

Diagnosis based on histopathology for skin cancer detection is today’s gold standard and relies on the presence or absence of biomarkers and cellular atypia. However it suffers drawbacks: it requires a strong expertise and is time-consuming. Moreover the notion of atypia or dysplasia of the visible cells used for diagnosis is very subjective, with poor inter-rater agreement reported in the literature. Lastly, histology requires a biopsy which is an invasive procedure and only captures a small sample of the lesion, which is insufficient in the context of large fields of cancerization. Here we demonstrate that the notion of cellular atypia can be objectively defined and quantified with a non-invasive in-vivo approach in three dimensions (3D). A Deep Learning (DL) algorithm is trained to segment keratinocyte (KC) nuclei from Line-field Confocal Optical Coherence Tomography (LC-OCT) 3D images. Based on these segmentations, a series of quantitative, reproducible and biologically relevant metrics is derived to describe KC nuclei individually. We show that, using those metrics, simple and more complex definitions of atypia can be derived to discriminate between healthy and pathological skins, achieving Area Under the ROC Curve (AUC) scores superior than 0.965, largely outperforming medical experts on the same task with an AUC of 0.766. All together, our approach and findings open the door to a precise quantitative monitoring of skin lesions and treatments, offering a promising non-invasive tool for clinical studies to demonstrate the effects of a treatment and for clinicians to assess the severity of a lesion and follow the evolution of pre-cancerous lesions over time.

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