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Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis

SIMPLE SUMMARY: We recently proved that in human colorectal cancer, the presence of small or large tumor-associated macrophages (TAMs) is associated with different outcomes. To translate this biological data into a robust clinical marker means to identify in a single slide all TAMs, hundreds of cell...

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Autores principales: Cancian, Pierandrea, Cortese, Nina, Donadon, Matteo, Di Maio, Marco, Soldani, Cristiana, Marchesi, Federica, Savevski, Victor, Santambrogio, Marco Domenico, Cerina, Luca, Laino, Maria Elena, Torzilli, Guido, Mantovani, Alberto, Terracciano, Luigi, Roncalli, Massimo, Di Tommaso, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269198/
https://www.ncbi.nlm.nih.gov/pubmed/34282750
http://dx.doi.org/10.3390/cancers13133313
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author Cancian, Pierandrea
Cortese, Nina
Donadon, Matteo
Di Maio, Marco
Soldani, Cristiana
Marchesi, Federica
Savevski, Victor
Santambrogio, Marco Domenico
Cerina, Luca
Laino, Maria Elena
Torzilli, Guido
Mantovani, Alberto
Terracciano, Luigi
Roncalli, Massimo
Di Tommaso, Luca
author_facet Cancian, Pierandrea
Cortese, Nina
Donadon, Matteo
Di Maio, Marco
Soldani, Cristiana
Marchesi, Federica
Savevski, Victor
Santambrogio, Marco Domenico
Cerina, Luca
Laino, Maria Elena
Torzilli, Guido
Mantovani, Alberto
Terracciano, Luigi
Roncalli, Massimo
Di Tommaso, Luca
author_sort Cancian, Pierandrea
collection PubMed
description SIMPLE SUMMARY: We recently proved that in human colorectal cancer, the presence of small or large tumor-associated macrophages (TAMs) is associated with different outcomes. To translate this biological data into a robust clinical marker means to identify in a single slide all TAMs, hundreds of cells, and then evaluate the area of each of them, a task unfeasible in the routine pathology workout. With the aim to develop a deep-learning pipeline to tackle this challenge, we selected, trained and tested three different approaches. The deep-learning pipeline based on the DeepLab-v3 architecture and semantic segmentation technique warrants the separation of TAMs from the background and the identification of single TAMs: this will easily allow the evaluation of their area. ABSTRACT: Quantitative analysis of Tumor Microenvironment (TME) provides prognostic and predictive information in several human cancers but, with few exceptions, it is not performed in daily clinical practice since it is extremely time-consuming. We recently showed that the morphology of Tumor Associated Macrophages (TAMs) correlates with outcome in patients with Colo-Rectal Liver Metastases (CLM). However, as for other TME components, recognizing and characterizing hundreds of TAMs in a single histopathological slide is unfeasible. To fasten this process, we explored a deep-learning based solution. We tested three Convolutional Neural Networks (CNNs), namely UNet, SegNet and DeepLab-v3, with three different segmentation strategies, semantic segmentation, pixel penalties and instance segmentation. The different experiments are compared according to the Intersection over Union (IoU), a metric describing the similarity between what CNN predicts as TAM and the ground truth, and the Symmetric Best Dice (SBD), which indicates the ability of CNN to separate different TAMs. UNet and SegNet showed intrinsic limitations in discriminating single TAMs (highest SBD [Formula: see text]), whereas DeepLab-v3 accurately recognized TAMs from the background (IoU [Formula: see text]) and separated different TAMs (SBD [Formula: see text]). This deep-learning pipeline to recognize TAMs in digital slides will allow the characterization of TAM-related metrics in the daily clinical practice, allowing the implementation of prognostic tools.
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spelling pubmed-82691982021-07-10 Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis Cancian, Pierandrea Cortese, Nina Donadon, Matteo Di Maio, Marco Soldani, Cristiana Marchesi, Federica Savevski, Victor Santambrogio, Marco Domenico Cerina, Luca Laino, Maria Elena Torzilli, Guido Mantovani, Alberto Terracciano, Luigi Roncalli, Massimo Di Tommaso, Luca Cancers (Basel) Article SIMPLE SUMMARY: We recently proved that in human colorectal cancer, the presence of small or large tumor-associated macrophages (TAMs) is associated with different outcomes. To translate this biological data into a robust clinical marker means to identify in a single slide all TAMs, hundreds of cells, and then evaluate the area of each of them, a task unfeasible in the routine pathology workout. With the aim to develop a deep-learning pipeline to tackle this challenge, we selected, trained and tested three different approaches. The deep-learning pipeline based on the DeepLab-v3 architecture and semantic segmentation technique warrants the separation of TAMs from the background and the identification of single TAMs: this will easily allow the evaluation of their area. ABSTRACT: Quantitative analysis of Tumor Microenvironment (TME) provides prognostic and predictive information in several human cancers but, with few exceptions, it is not performed in daily clinical practice since it is extremely time-consuming. We recently showed that the morphology of Tumor Associated Macrophages (TAMs) correlates with outcome in patients with Colo-Rectal Liver Metastases (CLM). However, as for other TME components, recognizing and characterizing hundreds of TAMs in a single histopathological slide is unfeasible. To fasten this process, we explored a deep-learning based solution. We tested three Convolutional Neural Networks (CNNs), namely UNet, SegNet and DeepLab-v3, with three different segmentation strategies, semantic segmentation, pixel penalties and instance segmentation. The different experiments are compared according to the Intersection over Union (IoU), a metric describing the similarity between what CNN predicts as TAM and the ground truth, and the Symmetric Best Dice (SBD), which indicates the ability of CNN to separate different TAMs. UNet and SegNet showed intrinsic limitations in discriminating single TAMs (highest SBD [Formula: see text]), whereas DeepLab-v3 accurately recognized TAMs from the background (IoU [Formula: see text]) and separated different TAMs (SBD [Formula: see text]). This deep-learning pipeline to recognize TAMs in digital slides will allow the characterization of TAM-related metrics in the daily clinical practice, allowing the implementation of prognostic tools. MDPI 2021-07-01 /pmc/articles/PMC8269198/ /pubmed/34282750 http://dx.doi.org/10.3390/cancers13133313 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cancian, Pierandrea
Cortese, Nina
Donadon, Matteo
Di Maio, Marco
Soldani, Cristiana
Marchesi, Federica
Savevski, Victor
Santambrogio, Marco Domenico
Cerina, Luca
Laino, Maria Elena
Torzilli, Guido
Mantovani, Alberto
Terracciano, Luigi
Roncalli, Massimo
Di Tommaso, Luca
Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title_full Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title_fullStr Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title_full_unstemmed Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title_short Development of a Deep-Learning Pipeline to Recognize and Characterize Macrophages in Colo-Rectal Liver Metastasis
title_sort development of a deep-learning pipeline to recognize and characterize macrophages in colo-rectal liver metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269198/
https://www.ncbi.nlm.nih.gov/pubmed/34282750
http://dx.doi.org/10.3390/cancers13133313
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