학술논문

Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration
Document Type
article
Source
JCI Insight. 4(8)
Subject
Heart Disease
Regenerative Medicine
Cardiovascular
Animals
Animals
Genetically Modified
Antibiotics
Antineoplastic
Cardiomyopathies
Disease Models
Animal
Doxorubicin
Echocardiography
Embryo
Nonmammalian
Feasibility Studies
Heart Ventricles
High-Throughput Screening Assays
Humans
Imaging
Three-Dimensional
Myocardial Contraction
Myocardium
Neoplasms
Receptors
Notch
Regeneration
Signal Transduction
Zebrafish
Cancer
Cardiology
Cardiovascular disease
Heart failure
Language
Abstract
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.