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

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 H Xu, Tzung K. Hsiai

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number8603
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Doxorubicin
Zebrafish
Light
Wounds and Injuries
Ventricular Dysfunction
Doppler Ultrasonography
Amyloid Precursor Protein Secretases
Ventricular Remodeling
Ventricular Function
Drug Discovery
Cardiomyopathies
Noise
Regeneration
Fishes
Drug Therapy
Injections
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair. / Packard, René R.Sevag; Baek, Kyung In; Beebe, Tyler; Jen, Nelson; DIng, Yichen; Shi, Feng; Fei, Peng; Kang, Bong Jin; Chen, Po Heng; Gau, Jonathan; Chen, Michael; Tang, Jonathan Y.; Shih, Yu Huan; DIng, Yonghe; Li, Debiao; Xu, Xiaolei H; Hsiai, Tzung K.

In: Scientific Reports, Vol. 7, No. 1, 8603, 01.12.2017.

Research output: Contribution to journalArticle

Packard, RRS, Baek, KI, Beebe, T, Jen, N, DIng, Y, Shi, F, Fei, P, Kang, BJ, Chen, PH, Gau, J, Chen, M, Tang, JY, Shih, YH, DIng, Y, Li, D, Xu, XH & Hsiai, TK 2017, 'Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair', Scientific Reports, vol. 7, no. 1, 8603. https://doi.org/10.1038/s41598-017-09152-x
Packard, René R.Sevag ; Baek, Kyung In ; Beebe, Tyler ; Jen, Nelson ; DIng, Yichen ; Shi, Feng ; Fei, Peng ; Kang, Bong Jin ; Chen, Po Heng ; Gau, Jonathan ; Chen, Michael ; Tang, Jonathan Y. ; Shih, Yu Huan ; DIng, Yonghe ; Li, Debiao ; Xu, Xiaolei H ; Hsiai, Tzung K. / Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{50be6b557d2a470e8020f010a24a7807,
title = "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. 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.",
author = "Packard, {Ren{\'e} R.Sevag} and Baek, {Kyung In} and Tyler Beebe and Nelson Jen and Yichen DIng and Feng Shi and Peng Fei and Kang, {Bong Jin} and Chen, {Po Heng} and Jonathan Gau and Michael Chen and Tang, {Jonathan Y.} and Shih, {Yu Huan} and Yonghe DIng and Debiao Li and Xu, {Xiaolei H} and Hsiai, {Tzung K.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-09152-x",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair

AU - Packard, René R.Sevag

AU - Baek, Kyung In

AU - Beebe, Tyler

AU - Jen, Nelson

AU - DIng, Yichen

AU - Shi, Feng

AU - Fei, Peng

AU - Kang, Bong Jin

AU - Chen, Po Heng

AU - Gau, Jonathan

AU - Chen, Michael

AU - Tang, Jonathan Y.

AU - Shih, Yu Huan

AU - DIng, Yonghe

AU - Li, Debiao

AU - Xu, Xiaolei H

AU - Hsiai, Tzung K.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85027890304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027890304&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-09152-x

DO - 10.1038/s41598-017-09152-x

M3 - Article

C2 - 28819303

AN - SCOPUS:85027890304

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8603

ER -