4.7 Article

Development and evaluation of deep learning-based segmentation of histologic structures in the kidney cortex with multiple histologic stains

Journal

KIDNEY INTERNATIONAL
Volume 99, Issue 1, Pages 86-101

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2020.07.044

Keywords

computerized morphologic assessment; deep learning; digital pathology; kidney histologic primitives; large-scale tissue interrogation; renal biopsy interpretation

Funding

  1. Case Western Reserve University (CWRU) Nephrology Training Grant [5T32DK007470-34]
  2. NephCure Kidney International/NEPTUNE pilot study
  3. NephCure/Smokler Gift to Duke University
  4. KidneyCure, ASN Foundation
  5. National Cancer Institute of the National Institutes of Health [1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01]
  6. National Institute of Biomedical Imaging and Bioengineering [1R43EB028736-01]
  7. National Center for Research Resources [1 C06 RR12463-01]
  8. VA Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service [IBX004121A]
  9. Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award [W81XWH-19-1-0668]
  10. DOD Prostate Cancer Idea Development Award [W81XWH-15-1-0558]
  11. DOD Lung Cancer Investigator-Initiated Translational Research Award [W81XWH-18-1-0440]
  12. DOD Peer Reviewed Cancer Research Program [W81XWH-16-1-0329]
  13. Ohio Third Frontier Technology Validation Fund
  14. Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering
  15. Clinical and Translational Science Award Program at Case Western Reserve University

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The application of deep learning for automated segmentation of histologic structures from kidney biopsies and nephrectomies showed that Periodic Acid Schiff-stained whole slide images yielded the best concordance between pathologists and deep learning segmentation. Silver stained whole slide images yielded the worst deep learning performance. This study represents the largest adaptation of deep learning for the segmentation of kidney histologic structures across multiple stains and pathology laboratories.
The application of deep learning for automated segmentation (delineation of boundaries) of histologic primitives (structures) from whole slide images can facilitate the establishment of novel protocols for kidney biopsy assessment. Here, we developed and validated deep learning networks for the segmentation of histologic structures on kidney biopsies and nephrectomies. For development, we examined 125 biopsies for Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 whole slide images stained with Hematoxylin & Eosin (125), Periodic Acid Schiff (125), Silver (102), and Trichrome (107) divided into training, validation and testing sets (ratio 6:1:3). Histologic structures were manually segmented (30048 total annotations) by five nephropathologists. Twenty deep learning models were trained with optimal digital magnification across the structures and stains. Periodic Acid Schiff-stained whole slide images yielded the best concordance between pathologists and deep learning segmentation across all structures (F-scores: 0.93 for glomerular tufts, 0.94 for glomerular tuft plus Bowman's capsule, 0.91 for proximal tubules, 0.93 for distal tubular segments, 0.81 for peritubular capillaries, and 0.85 for arteries and afferent arterioles). Optimal digital magnifications were 5X for glomerular tuft/tuft plus Bowman's capsule, 10X for proximal/distal tubule, arteries and afferent arterioles, and 40X for peritubular capillaries. Silver stained whole slide images yielded the worst deep learning performance. Thus, this largest study to date adapted deep learning for the segmentation of kidney histologic structures across multiple stains and pathology laboratories. All data used for training and testing and a detailed online tutorial will be publicly available.

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