Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair

Abstract This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair...

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Autores principales: René R. Sevag Packard, Kyung In Baek, Tyler Beebe, Nelson Jen, Yichen Ding, Feng Shi, Peng Fei, Bong Jin Kang, Po-Heng Chen, Jonathan Gau, Michael Chen, Jonathan Y. Tang, Yu-Huan Shih, Yonghe Ding, Debiao Li, Xiaolei Xu, Tzung K. Hsiai
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:cf8a7b60f3f1442096de0430ac596c002021-12-02T11:40:59ZAutomated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair10.1038/s41598-017-09152-x2045-2322https://doaj.org/article/cf8a7b60f3f1442096de0430ac596c002017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09152-xhttps://doaj.org/toc/2045-2322Abstract This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7–19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9–20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6–14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.René R. Sevag PackardKyung In BaekTyler BeebeNelson JenYichen DingFeng ShiPeng FeiBong Jin KangPo-Heng ChenJonathan GauMichael ChenJonathan Y. TangYu-Huan ShihYonghe DingDebiao LiXiaolei XuTzung K. HsiaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
René R. Sevag Packard
Kyung In Baek
Tyler Beebe
Nelson Jen
Yichen Ding
Feng Shi
Peng Fei
Bong Jin Kang
Po-Heng Chen
Jonathan Gau
Michael Chen
Jonathan Y. Tang
Yu-Huan Shih
Yonghe Ding
Debiao Li
Xiaolei Xu
Tzung K. Hsiai
Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
description Abstract This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7–19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9–20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6–14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.
format article
author René R. Sevag Packard
Kyung In Baek
Tyler Beebe
Nelson Jen
Yichen Ding
Feng Shi
Peng Fei
Bong Jin Kang
Po-Heng Chen
Jonathan Gau
Michael Chen
Jonathan Y. Tang
Yu-Huan Shih
Yonghe Ding
Debiao Li
Xiaolei Xu
Tzung K. Hsiai
author_facet René R. Sevag Packard
Kyung In Baek
Tyler Beebe
Nelson Jen
Yichen Ding
Feng Shi
Peng Fei
Bong Jin Kang
Po-Heng Chen
Jonathan Gau
Michael Chen
Jonathan Y. Tang
Yu-Huan Shih
Yonghe Ding
Debiao Li
Xiaolei Xu
Tzung K. Hsiai
author_sort René R. Sevag Packard
title Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
title_short Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
title_full Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
title_fullStr Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
title_full_unstemmed Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
title_sort automated segmentation of light-sheet fluorescent imaging to characterize experimental doxorubicin-induced cardiac injury and repair
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/cf8a7b60f3f1442096de0430ac596c00
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