The neonatal mouse heart in contrast to the adults has the ability to regenerate after myocardial infarction. The investigation of cardiac morphogenesis is critical to uncover the underlying mechanism of cardiac regeneration. Hence, we have developed a light-sheet microscope (LSM) along with the tissue-clearing method to investigate the 3-dimensional (3D) architecture of the intact neonatal mouse heart. We improved our imaging system by incorporating an axially swept remote focusing arm with a voice coil actuator for isotropic imaging. Our LSM offers a lateral resolution of 2.08 ± 0.11 μm and an axial resolution of 2.84 ± 0.19 μm. Using this strategy, we can take optical sections throughout the intact heart and enabling us to reveal the cardiac structure of the neonatal mouse.
Paroxysmal arrhythmias caused by medications are challenging to be prospectively identified. Zebrafish have emerged as an ideal model organism for screening small molecule compounds to study cardiac abnormalities, due to their rapid development, optical transparency during early stages, and similarities to the human heart. To overcome the challenges associated with observing cardiac abnormalities in zebrafish, we sought to develop a light-field microscope, a rapid imaging method with high photon efficiency, for the volumetric acquisition in a single snapshot. This method, along with its variations, utilizes a multi-lens array (MLA) to capture angular information. We have customized a light-field system and developed a pipeline to incorporate the MLA into the detection path. A program based on wave optics has also been developed to calculate the point spread function at different depths. The program involves two main steps: calculating the wide-field PSF and applying the MLA effect as a mask. This enables us to simulate the impact of the MLA on the imaging system. The comparison between the simulated and experimental data allows for the determination of MLA position. We aim to capture drug-induced arrhythmias in zebrafish larvae using this method, exploring the contractile dysfunction across the atrium and ventricle during multiple cardiac cycles. This research aims to deepen our understanding of the mechanisms underlying these arrhythmias and their connection to drug effects.
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