RhythmWriter: GPU-accelerated Contractility Quantification for Large Datasets

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been considered optimal model systems for use in cardiac safety testing, yet their adoption remains low, largely because of technical limitations in the analysis methodology. RhythmWriter (RW) is an open-source GPU plugin for ImageJ developed to quantify contractile motion over extended periods of time. RW compensates for baseline drift, is time-scale invariant and is capable of very rapid data analysis. As a consequence, RW is capable of generating simultaneous high-resolution contraction restitution curves from multiple aggregates of hiPSC-CMs derived from premature-stimulus (S1S2) and dynamic-ramp restitution protocols. The aggregates exhibit brief refractory periods, which allow the induction of S2 beats at coupling intervals down to 130 ms and 1:1 entrainment during periodic stimulation down to a cycle length of 245 ms. Simulations confirm the ability of RW to track programmed contractile strength and stimulation intervals even at rapid pacing rates. This makes possible, for the first time, high-throughput functional assessment of hiPSC-CM aggregates for contractility drug screening and maturation.