Automated detection and analysis of depolarization events in human cardiomyocytes using MaDEC.
Optical imaging-based methods for assessing the membrane electrophysiology of in vitro human cardiac cells allow for non-invasive temporal assessment of the effect of drugs and other stimuli. Automated methods for detecting and analyzing the depolarization events (DEs) in image-based data allow quantitative assessment of these different treatments. In this study, we use 2-photon microscopy of fluorescent voltage-sensitive dyes (VSDs) to capture the membrane voltage of actively beating human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). We built a custom and freely available Matlab software, called MaDEC, to detect, quantify, and compare DEs of hiPS-CMs treated with the β-adrenergic drugs, propranolol and isoproterenol. The efficacy of our software is quantified by comparing detection results against manual DE detection by expert analysts, and comparing DE analysis results to known drug-induced electrophysiological effects. The software accurately detected DEs with true positive rates of 98-100% and false positive rates of 1-2%, at signal-to-noise ratios (SNRs) of 5 and above. The MaDEC software was also able to distinguish control DEs from drug-treated DEs both immediately as well as 10min after drug administration.
Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA. Electronic address: aggie.szymanska@gmail.com.
Agnieszka F
AF
Szymanska
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
Christopher
C
Heylman
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
Rupsa
R
Datta
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
Enrico
E
Gratton
Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
Zoran
Z
Nenadic
D001330:Electronic Data Processing / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D012984:Software
D011433:Propranolol; D007545:Isoproterenol
Classification; Matched filter; Signal detection; Voltage-sensitive dye imaging; hiPS derived cardiomyocytes