Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays

Abstract This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid respo...

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Main Authors: Christophe Deben, Edgar Cardenas De La Hoz, Felicia Rodrigues Fortes, Maxim Le Compte, Sofie Seghers, Steve Vanlanduit, Hendrik Vercammen, Bert Van Den Bogert, Nelson Dusetti, Abraham Lin, Geert Roeyen, Marc Peeters, Hans Prenen, Filip Lardon, Evelien Smits
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07329-5
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author Christophe Deben
Edgar Cardenas De La Hoz
Felicia Rodrigues Fortes
Maxim Le Compte
Sofie Seghers
Steve Vanlanduit
Hendrik Vercammen
Bert Van Den Bogert
Nelson Dusetti
Abraham Lin
Geert Roeyen
Marc Peeters
Hans Prenen
Filip Lardon
Evelien Smits
author_facet Christophe Deben
Edgar Cardenas De La Hoz
Felicia Rodrigues Fortes
Maxim Le Compte
Sofie Seghers
Steve Vanlanduit
Hendrik Vercammen
Bert Van Den Bogert
Nelson Dusetti
Abraham Lin
Geert Roeyen
Marc Peeters
Hans Prenen
Filip Lardon
Evelien Smits
author_sort Christophe Deben
collection DOAJ
description Abstract This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid responses to anticancer treatments but face limitations in accurately quantifying cytostatic and cytotoxic effects across varying growth rates. Here, we introduce the Normalized Organoid Growth Rate (NOGR) metric, specifically developed for brightfield imaging-based assays. A label-free image analysis model was applied to segment organoids precisely, track their growth rates over time, and classify viable and dead organoids. Testing eleven phenotypically distinct pancreatic cancer organoid models with five chemotherapeutics demonstrates that the NOGR metric more effectively captures cytostatic and cytotoxic drug effects compared to existing methods. This approach enhances the biological relevance of drug sensitivity assessments on organoids and offers a valuable tool for advancing personalized cancer treatment strategies.
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spelling doaj-art-ccaa7af0afca4fca9dfbdb7f330730872025-08-20T02:30:59ZengNature PortfolioCommunications Biology2399-36422024-12-017111110.1038/s42003-024-07329-5Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assaysChristophe Deben0Edgar Cardenas De La Hoz1Felicia Rodrigues Fortes2Maxim Le Compte3Sofie Seghers4Steve Vanlanduit5Hendrik Vercammen6Bert Van Den Bogert7Nelson Dusetti8Abraham Lin9Geert Roeyen10Marc Peeters11Hans Prenen12Filip Lardon13Evelien Smits14Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpIndustrial Vision Lab, University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpIndustrial Vision Lab, University of AntwerpAntwerp Research Group for Ocular Science (ARGOS), Translational Neurosciences, Faculty of Medicine and Health Sciences, University of AntwerpAntwerp Research Group for Ocular Science (ARGOS), Translational Neurosciences, Faculty of Medicine and Health Sciences, University of AntwerpCentre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-CalmettesCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of AntwerpAbstract This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid responses to anticancer treatments but face limitations in accurately quantifying cytostatic and cytotoxic effects across varying growth rates. Here, we introduce the Normalized Organoid Growth Rate (NOGR) metric, specifically developed for brightfield imaging-based assays. A label-free image analysis model was applied to segment organoids precisely, track their growth rates over time, and classify viable and dead organoids. Testing eleven phenotypically distinct pancreatic cancer organoid models with five chemotherapeutics demonstrates that the NOGR metric more effectively captures cytostatic and cytotoxic drug effects compared to existing methods. This approach enhances the biological relevance of drug sensitivity assessments on organoids and offers a valuable tool for advancing personalized cancer treatment strategies.https://doi.org/10.1038/s42003-024-07329-5
spellingShingle Christophe Deben
Edgar Cardenas De La Hoz
Felicia Rodrigues Fortes
Maxim Le Compte
Sofie Seghers
Steve Vanlanduit
Hendrik Vercammen
Bert Van Den Bogert
Nelson Dusetti
Abraham Lin
Geert Roeyen
Marc Peeters
Hans Prenen
Filip Lardon
Evelien Smits
Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
Communications Biology
title Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
title_full Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
title_fullStr Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
title_full_unstemmed Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
title_short Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
title_sort development and validation of the normalized organoid growth rate nogr metric in brightfield imaging based assays
url https://doi.org/10.1038/s42003-024-07329-5
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