ZFIN ID: ZDB-PUB-170819-3
Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
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.
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.
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.