Computer-assisted mitotic count using a deep learning-based algorithm improves interobserver reproducibility and accuracy.

Journal: Veterinary pathology
Published Date:

Abstract

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs.

Authors

  • Christof A Bertram
    Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • Marc Aubreville
    Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. marc.aubreville@fau.de.
  • Taryn A Donovan
    Animal Medical Center, New York, NY, USA.
  • Alexander Bartel
    Freie Universität Berlin, Berlin, Germany.
  • Frauke Wilm
    Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Christian Marzahl
    Pattern Recognition Lab, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. c.marzahl@euroimmun.de.
  • Charles-Antoine Assenmacher
    University of Pennsylvania, Philadelphia, PA, USA.
  • Kathrin Becker
    University of Veterinary Medicine, Hannover, Germany.
  • Mark Bennett
    Synlab's VPG Histology, Bristol, UK.
  • Sarah Corner
    Michigan State University, Lansing, MI, USA.
  • Brieuc Cossic
    Roche, Pharmaceutical Research and Early Development (pRED), Roche Innovation Center, Basel, Switzerland.
  • Daniela Denk
    Ludwig Maximilians University, Munich, Germany.
  • Martina Dettwiler
    University of Bern, Bern, Switzerland.
  • Beatriz Garcia Gonzalez
    Synlab's VPG Histology, Bristol, UK.
  • Corinne Gurtner
    University of Bern, Bern, Switzerland.
  • Ann-Kathrin Haverkamp
    University of Veterinary Medicine, Hannover, Germany.
  • Annabelle Heier
    IDEXX Vet Med Labor GmbH, Kornwestheim, Germany.
  • Annika Lehmbecker
    IDEXX Vet Med Labor GmbH, Kornwestheim, Germany.
  • Sophie Merz
    IDEXX Vet Med Labor GmbH, Kornwestheim, Germany.
  • Erica L Noland
    Michigan State University, Lansing, MI, USA.
  • Stephanie Plog
    Synlab's VPG Histology, Bristol, UK.
  • Anja Schmidt
    IDEXX Vet Med Labor GmbH, Kornwestheim, Germany.
  • Franziska Sebastian
    IDEXX Vet Med Labor GmbH, Kornwestheim, Germany.
  • Dodd G Sledge
    Michigan State University, Lansing, MI, USA.
  • Rebecca C Smedley
    Michigan State University, Lansing, MI, USA.
  • Marco Tecilla
    Roche Pharmaceutical Research and Early Development (pRED), Basel, Switzerland.
  • Tuddow Thaiwong
    Michigan State University, Lansing, MI, USA.
  • Andrea Fuchs-Baumgartinger
    University of Veterinary Medicine, Vienna, Austria.
  • Donald J Meuten
    North Carolina State University, Raleigh, NC, USA.
  • Katharina Breininger
  • Matti Kiupel
    Michigan State University, Lansing, MI, USA.
  • Andreas Maier
    Pattern Recognition Lab, University Erlangen-Nürnberg, Erlangen, Germany.
  • Robert Klopfleisch
    Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.