Automated multi-parameter measurement of cardiomyocytes dynamics with digital holographic microscopy

Abstract

Abstract:Compounds tested during drug development may have adverse effects on the heart; therefore all new chemical entities have to undergo extensive preclinical assessment for cardiac liability. Conventional intensity-based imaging techniques are not robust enough to provide detailed information for cell structure and the captured images result in lowcontrast, especially to cell with semi-transparent or transparent feature, which would affect the cell analysis. In this paper we show, for the first time, that digital holographic microscopy (DHM) integrated with information processing algorithms automatically provide dynamic quantitative phase profiles of beating cardiomyocytes. We experimentally demonstrate that relevant parameters of cardiomyocytes can be obtained by our automated algorithm based on DHM phase signal analysis and used to characterize the physiological state of resting cardiomyocytes. Our study opens the possibility of automated quantitative analysis of cardiomyocyte dynamics suitable for further drug safety testing and compounds selection as a new paradigm in drug toxicity screens.

Automated quantitative analysis of multiple cardiomyocytes at the single‐cell level with three‐dimensional holographic imaging informatics

“…Thus, the spatial changes between consecutive frames were measured. Table shows that our result is consistent with those reported in our previous work .…”

“…(Madison, Wisconsin), were cultured and grown according to the manufacturer's instructions for 14 days before images were recorded. Measurements were acquired in a Chamlide WP incubator system with a 96‐well plate (LCI, Seoul, South Korea) set at 37°/5% CO 2 at high humidity .…”

“…The segmented region includes a small area of the cytoplasm which nucleus is enclosed. The main difference between this work and the previous published work is that the signal provided by the whole image might be less informative than each single segmented cell because of the non‐beating background region, etc. In addition, this work is potential to be used for the analysis of cell‐to‐cell synchronization.…”

“…(Madison, Wisconsin), were cultured and grown according to the manufacturer's instructions for 14 days before images were recorded. Measurements were acquired in a Chamlide WP incubator system with a 96-well plate (LCI, Seoul, South Korea) set at 37 /5% CO 2 at high humidity [24]. The k-means technique is among the most popular clustering methods suitable for biomedical image segmentation, and is commonly applied when grouping pixels in images or video sequences [25][26][27].…”

Phenotypic assays for analyses of pluripotent stem cell–derived cardiomyocytes

“…The images can also be analyzed using Fourier transform traction cytometry to quantify the contraction force . Rappaz et al have reported the possibilities of digital holographic microscopy to be used as an efficient tool for complex CM beating analysis by thickness quantitative measurement …”