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

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.

SUBMITTER: Chen J

PROVIDER: S-EPMC6538350 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Chen Junjie J Ding Yichen Y Chen Michael M Gau Jonathan J Jen Nelson N Nahal Chadi C Tu Sally S Chen Cynthia C Zhou Steve S Chang Chih-Chiang CC Lyu Jintian J Xu Xiaolei X Hsiai Tzung K TK Packard René R Sevag RRS

JCI insight 20190418 8

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 mi ...[more]

PMID: 30996130

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Project description:Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation that reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis by using transthoracic echocardiography are (mean ± SD) -19.7% ± 0.4%, while radial and circumferential strain are 47.3% ± 1.9% and -23.3% ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages -1.10 ± 0.16 s. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to assess components of myocardial systolic and diastolic function. Myocardial deformation analysis is based on either Doppler or a non-Doppler technique, called speckle-tracking echocardiography. Myocardial deformation analysis provides quantitative measures of global and regional myocardial function for use in the perioperative care of the surgical patient. For example, coronary graft occlusion after coronary artery bypass grafting is detected by an acute reduction in strain in the affected coronary artery territory. In addition, assessment of left ventricular mechanics detects underlying myocardial pathology before abnormalities become apparent on conventional echocardiography. Certainly, patients with aortic regurgitation demonstrate reduced longitudinal strain before reduction in LVEF occurs, which allows detection of subclinical left ventricular dysfunction and predicts increased risk for heart failure and impaired myocardial function after surgical repair. In this review, we describe the principles, techniques, and clinical application of myocardial deformation analysis.

Dataset Information

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

Publications

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

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