PUBLICATION
Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
- Authors
- Packard, R.R.S., Baek, K.I., Beebe, T., Jen, N., Ding, Y., Shi, F., Fei, P., Kang, B.J., Chen, P.H., Gau, J., Chen, M., Tang, J.Y., Shih, Y.H., Ding, Y., Li, D., Xu, X., Hsiai, T.K.
- ID
- ZDB-PUB-170819-3
- Date
- 2017
- Source
- Scientific Reports 7: 8603 (Journal)
- Registered Authors
- Ding, Yonghe, Shih, Yu-huan, Xu, Xiaolei
- Keywords
- Cardiac regeneration, Cardiovascular models
- MeSH Terms
-
- Animals
- Automation
- Doxorubicin/adverse effects*
- Fluorescence
- Heart Injuries/chemically induced*
- Heart Injuries/diagnostic imaging*
- Heart Injuries/genetics
- Heart Injuries/physiopathology
- Imaging, Three-Dimensional*
- Myocardium/pathology
- Receptors, Notch/metabolism
- Regeneration*/drug effects
- Signal Transduction/drug effects
- Zebrafish
- PubMed
- 28819303 Full text @ Sci. Rep.
Citation
Packard, R.R.S., Baek, K.I., Beebe, T., Jen, N., Ding, Y., Shi, F., Fei, P., Kang, B.J., Chen, P.H., Gau, J., Chen, M., Tang, J.Y., Shih, Y.H., Ding, Y., Li, D., Xu, X., Hsiai, T.K. (2017) Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair. Scientific Reports. 7:8603.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping