MUSCLEMOTION

Author:

Sala Luca1,van Meer Berend J.1,Tertoolen Leon G.J.1,Bakkers Jeroen1,Bellin Milena1,Davis Richard P.1,Denning Chris1,Dieben Michel A.E.1,Eschenhagen Thomas1,Giacomelli Elisa1,Grandela Catarina1,Hansen Arne1,Holman Eduard R.1,Jongbloed Monique R.M.1,Kamel Sarah M.1,Koopman Charlotte D.1,Lachaud Quentin1,Mannhardt Ingra1,Mol Mervyn P.H.1,Mosqueira Diogo1,Orlova Valeria V.1,Passier Robert1,Ribeiro Marcelo C.1,Saleem Umber1,Smith Godfrey L.1,Burton Francis L.1,Mummery Christine L.1

Affiliation:

1. From the Department of Anatomy and Embryology, Leiden University Medical Center, The Netherlands (L.S., B.J.v.M., L.G.J.T., M.B., R.P.D., M.A.E.D., E.G., C.G., M.R.M.J., M.P.H.M., V.V.O., R.P., C.L.M.); Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary, and Life Science, University of Glasgow, United Kingdom (Q.L., G.L.S., F.L.B.); Hubrecht Institute – Royal Netherlands Academy of Arts and Sciences, Utrecht, The Netherlands (J.B., S.M.K., C.D.K.); Department of Stem...

Abstract

Rationale: There are several methods to measure cardiomyocyte and muscle contraction, but these require customized hardware, expensive apparatus, and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming, and only specialist researchers can quantify data. Objective: Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses. Methods and Results: MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac “organoids,” engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses. Conclusions: Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

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