ZFIN ID: ZDB-PUB-190422-2
Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration
Chen, J., Ding, Y., Chen, M., Gau, J., Jen, N., Nahal, C., Tu, S., Chen, C., Zhou, S., Chang, C.C., Lyu, J., Xu, X., Hsiai, T.K., Packard, R.R.S.
Date: 2019
Source: JCI insight   4(8): (Review)
Registered Authors: Xu, Xiaolei
Keywords: Cancer, Cardiology, Cardiovascular disease, Heart failure
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Antibiotics, Antineoplastic/adverse effects*
  • Cardiomyopathies/chemically induced*
  • Cardiomyopathies/diagnostic imaging
  • Cardiomyopathies/physiopathology
  • Disease Models, Animal
  • Doxorubicin/adverse effects*
  • Echocardiography
  • Embryo, Nonmammalian
  • Feasibility Studies
  • Heart Ventricles/diagnostic imaging*
  • Heart Ventricles/drug effects
  • Heart Ventricles/physiopathology
  • High-Throughput Screening Assays/methods
  • Humans
  • Imaging, Three-Dimensional/methods*
  • Myocardial Contraction/drug effects
  • Myocardium/pathology
  • Neoplasms/drug therapy
  • Receptors, Notch/metabolism
  • Regeneration/drug effects
  • Signal Transduction/drug effects
  • Zebrafish
PubMed: 30996130 Full text @ JCI Insight
Zebrafish are increasingly utilized to model cardiomyopathies and regeneration. Current methods evaluating cardiac function have known limitations, fail to reliably detect focal mechanics, and are not readily feasible in zebrafish. We developed a semiautomated, open-source method - displacement analysis of myocardial mechanical deformation (DIAMOND) - for quantitative assessment of 4D segmental cardiac function. We imaged transgenic embryonic zebrafish in vivo using a light-sheet fluorescence microscopy system with 4D cardiac motion synchronization. Our method permits the derivation of a transformation matrix to quantify the time-dependent 3D displacement of segmental myocardial mass centroids. Through treatment with doxorubicin, and by chemically and genetically manipulating the myocardial injury-activated Notch signaling pathway, we used DIAMOND to demonstrate that basal ventricular segments adjacent to the atrioventricular canal display the highest 3D displacement and are also the most susceptible to doxorubicin-induced injury. Thus, DIAMOND provides biomechanical insights into in vivo segmental cardiac function scalable to high-throughput research applications.