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Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration
Junjie Chen, … , Tzung K. Hsiai, René R. Sevag Packard
Junjie Chen, … , Tzung K. Hsiai, René R. Sevag Packard
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(8):e125362. https://doi.org/10.1172/jci.insight.125362.
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Resource and Technical Advance Cardiology

Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration

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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.

Authors

Junjie Chen, Yichen Ding, Michael Chen, Jonathan Gau, Nelson Jen, Chadi Nahal, Sally Tu, Cynthia Chen, Steve Zhou, Chih-Chiang Chang, Jintian Lyu, Xiaolei Xu, Tzung K. Hsiai, René R. Sevag Packard

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Figure 1

DIAMOND displacement analysis of focal myocardial mechanical deformation.

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DIAMOND displacement analysis of focal myocardial mechanical deformation...
Raw images were captured by light-sheet fluorescent microscopy (LSFM) (A) to reconstruct the digital 3D myocardium and resampled along the true anatomic short axis of the ventricle (B and C). The ventricle in the schematic illustration (D) is divided into 8 segments and delineated into 6 segments with exclusion of the atrioventricular valve area (E, 2D; and F, 3D) due to relative paucity of myocardial tissue. A reference matrix from the initial resampled condition in systole was used for the reorientation of subsequent matrices (G) and registration of all the resampled slices. A group of rectangular parallelepipeds was used for the generation of transformation matrix (Tm) (H) from end-diastole to end-systole. The diastolic and systolic myocardium in the same global coordinate system were well registered by applying Tm to diastole (I). 3D myocardial displacements of a single segment (J) is illustrated from end-systole to end-diastole in a control myocardium. 3D displacement vectors of sequential consecutive deformations (K) and end-to-end displacement of 6 myocardial segments from end-systole to end-diastole are depicted by DIAMOND (L).

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