Convolutional Neural Networks for the Evaluation of Chronic and Inflammatory Lesions in Kidney Transplant Biopsies
Hermsen, Meyke; Ciompi, Francesco; Adefidipe, Adeyemi; Denic, Aleksandar; Dendooven, Amélie; Smith, Byron H; van Midden, Dominique; Bräsen, Jan Hinrich; Kers, Jesper; Stegall, Mark D; Bándi, Péter; Nguyen, Tri; Swiderska-Chadaj, Zaneta; Smeets, Bart; Hilbrands, Luuk B; van der Laak, Jeroen A W M
(2022) American Journal of Pathology, volume 192, issue 10, pp. 1418 - 1432
(Article)
Abstract
In kidney transplant biopsies, both inflammation and chronic changes are important features that predict long-term graft survival. Quantitative scoring of these features is important for transplant diagnostics and kidney research. However, visual scoring is poorly reproducible and labor intensive. The goal of this study was to investigate the potential of
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convolutional neural networks (CNNs) to quantify inflammation and chronic features in kidney transplant biopsies. A structure segmentation CNN and a lymphocyte detection CNN were applied on 125 whole-slide image pairs of periodic acid-Schiff- and CD3-stained slides. The CNN results were used to quantify healthy and sclerotic glomeruli, interstitial fibrosis, tubular atrophy, and inflammation within both nonatrophic and atrophic tubuli, and in areas of interstitial fibrosis. The computed tissue features showed high correlation with Banff lesion scores of five pathologists (A.A., A.Dend., J.H.B., J.K., and T.N.). Analyses on a small subset showed a moderate correlation toward higher CD3<sup>+</sup> cell density within scarred regions and higher CD3<sup>+</sup> cell count inside atrophic tubuli correlated with long-term change of estimated glomerular filtration rate. The presented CNNs are valid tools to yield objective quantitative information on glomeruli number, fibrotic tissue, and inflammation within scarred and non-scarred kidney parenchyma in a reproducible manner. CNNs have the potential to improve kidney transplant diagnostics and will benefit the community as a novel method to generate surrogate end points for large-scale clinical studies.
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Keywords: Atrophy/pathology, Biomarkers, Biopsy, Fibrosis, Graft vs Host Disease/pathology, Humans, Inflammation/pathology, Kidney Transplantation, Kidney/pathology, Neural Networks, Computer, Periodic Acid, Pathology and Forensic Medicine, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 0002-9440
Publisher: Elsevier
Note: Funding Information: Supported by the ERACoSysMed initiative (SysMIFTA project) as part of the European Union's Horizon 2020 Framework Program offered by ZonMw through grant 9003035004 (M.H.) and by the Dutch Kidney Foundation through grants 17OKG23 (DEEPGRAFT project) (J.K.) and 21OK+012 (DIAGGRAFT project) (M.H. and D.v.M.). The development of the lymphocyte detection network and the automated analysis pipeline was supported by the Dutch Cancer Society grant KUN 2014-7032 (Alpe d'HuZes AQUILA project) (F.C. and Z.S.-C.). Funding Information: Supported by the ERACoSysMed initiative (SysMIFTA project) as part of the European Union's Horizon 2020 Framework Program offered by ZonMw through grant 9003035004 (M.H.) and by the Dutch Kidney Foundation through grants 17OKG23 (DEEPGRAFT project) (J.K.) and 21OK+012 (DIAGGRAFT project) (M.H. and D.v.M.). The development of the lymphocyte detection network and the automated analysis pipeline was supported by the Dutch Cancer Society grant KUN 2014-7032 (Alpe d'HuZes AQUILA project) (F.C. and Z.S.-C.). Disclosures: J.A.W.M.v.d.L. is a member of the advisory boards of Philips, the Netherlands, and ContextVision, Sweden, and received research funding from Philips, the Netherlands, ContextVision, Sweden, and Sectra, Sweden, in the last 5 years. He is chief scientific officer and shareholder of Aiosyn BV, the Netherlands. F.C. is advisory board member and shareholder of Aiosyn BV, the Netherlands, and received consulting fees from TRIBVN Healthcare, France. Publisher Copyright: © 2022 American Society for Investigative Pathology
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