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

Author:

Bertram Christof A.12ORCID,Aubreville Marc3ORCID,Donovan Taryn A.4ORCID,Bartel Alexander2ORCID,Wilm Frauke5,Marzahl Christian5,Assenmacher Charles-Antoine6,Becker Kathrin7ORCID,Bennett Mark8,Corner Sarah9,Cossic Brieuc10,Denk Daniela11,Dettwiler Martina12ORCID,Gonzalez Beatriz Garcia8,Gurtner Corinne12,Haverkamp Ann-Kathrin7,Heier Annabelle13ORCID,Lehmbecker Annika13,Merz Sophie13,Noland Erica L.9,Plog Stephanie8,Schmidt Anja13,Sebastian Franziska13,Sledge Dodd G.9,Smedley Rebecca C.9ORCID,Tecilla Marco14,Thaiwong Tuddow9,Fuchs-Baumgartinger Andrea1,Meuten Donald J.15,Breininger Katharina5,Kiupel Matti9,Maier Andreas5,Klopfleisch Robert2ORCID

Affiliation:

1. University of Veterinary Medicine, Vienna, Austria

2. Freie Universität Berlin, Berlin, Germany

3. Technische Hochschule Ingolstadt, Ingolstadt, Germany

4. Animal Medical Center, New York, NY, USA

5. Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

6. University of Pennsylvania, Philadelphia, PA, USA

7. University of Veterinary Medicine, Hannover, Germany

8. Synlab’s VPG Histology, Bristol, UK

9. Michigan State University, Lansing, MI, USA

10. Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland

11. Ludwig Maximilians University, Munich, Germany

12. University of Bern, Bern, Switzerland

13. IDEXX Vet Med Labor GmbH, Kornwestheim, Germany

14. Roche Pharmaceutical Research and Early Development (pRED), Basel, Switzerland

15. North Carolina State University, Raleigh, NC, USA

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.

Publisher

SAGE Publications

Subject

General Veterinary

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