The present paper by Rappaz et al. reports an exciting development in this direction. The authors develop an approach for automated and rapid analysis of dynamics of cultured cardiomyocytes without using any external label. They rely on quantitative measurement of morphology of cardiomyocytes in terms of their optical path length. Using digital holographic microscopy (DHM) and computational algorithms, they retrieve optical path length of a large number of cardiomyocytes from a single snapshot. From time-series of optical path length, they extract periodic contractions of cardiomyocytes. By fitting the temporal profiles of optical path length with expected beat pattern, they estimate key parameters of the beat cycle. This is a promising approach for high throughput screening of effects of drugs on the contractile function of cardiomyocytes.
These results point towards exciting possibilities: 1) the resolution of morphological imaging can be improved using phase imaging methods that use angularly diverse illumination, instead of collimated illumination required for DHM. Recent advances in programmed illumination should allow such measurements without sacrificing speed. 2) Morphological measurements with DHM or other quantitative phase imaging schemes are promising means of assessing drugs that affect cell cycle, such as cancer drugs. 3) Extending this approach to functional imaging of beating heart requires optical sectioning, which remains an open challenge in phase microscopy. With imaging modes that permit optical sectioning, such as fluorescence microscopy, computational imaging algorithms that exploit periodicity of the heart-beat permit extraction of both functional and three dimensional morphological information. A challenging yet exciting goal for the field is to retrieve functional parameters of multiple organs in a vertebrate disease model with a fully sequenced genome, e.g., zebrafish.
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