Key result
Dual optical imaging reveals hiPSC-CM mechanical waves break down earlier than electrical waves.
Why the study?
Optical mapping of electrical waves using fluorescent labels provides mechanistic insights into conduction abnormalities, but dye-free mapping of mechanical waves offers a non-invasive alternative.
A novel simultaneous voltage and dye-free optical imaging method enables low-cost, non-invasive quantification of electromechanical waves in hiPSC-CMs for cardiotoxicity testing and drug development.
Supports preclinical electromechanical mapping in hiPSC-CMs for drug screening; leaves open translation to clinical arrhythmia assessment.
Coupled electromechanical waves define a heart's function in health and diseases. Optical mapping of electrical waves using fluorescent labels offers mechanistic insights into cardiac conduction abnormalities. Dye-free/label-free mapping of mechanical waves presents an attractive non-invasive alternative. In this study, we developed a simultaneous widefield voltage and interferometric dye-free optical imaging methodology that was used as follows: (1) to validate dye-free optical mapping for quantification of cardiac wave properties in human iPSC-cardiomyocytes (CMs); (2) to demonstrate low-cost optical mapping of electromechanical waves in hiPSC-CMs using recent near-infrared (NIR) voltage sensors and orders of magnitude cheaper miniature industrial CMOS cameras; (3) to uncover previously underexplored frequency- and space-varying parameters of cardiac electromechanical waves in hiPSC-CMs. We find similarity in the frequency-dependent responses of electrical (NIR fluorescence-imaged) and mechanical (dye-free-imaged) waves, with the latter being more sensitive to faster rates and showing steeper restitution and earlier appearance of wavefront tortuosity. During regular pacing, the dye-free-imaged conduction velocity and electrical wave velocity are correlated; both modalities are sensitive to pharmacological uncoupling and dependent on gap-junctional protein (connexins) determinants of wave propagation. We uncover the strong frequency dependence of the electromechanical delay (EMD) locally and globally in hiPSC-CMs on a rigid substrate. The presented framework and results offer new means to track the functional responses of hiPSC-CMs inexpensively and non-invasively for counteracting heart disease and aiding cardiotoxicity testing and drug development.
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Liu et al. (2023) studied Cardiac electromechanical wave model (hiPSC-CMs) (n=6). Simultaneous widefield voltage and dye-free optical mapping was evaluated on Quantification of electrical and mechanical wave properties under spontaneous and paced conditions. Simultaneous widefield voltage and dye-free optical imaging successfully mapped electromechanical waves in hiPSC-CMs, revealing that mechanical waves are more sensitive to faster pacing rates and show steeper restitution and earlier wavefront tortuosity compared to electrical waves.
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