Axially swept dithered light-sheet microscope to reveal cardiac morphology

Almasian, M.; Saberigarakani, A.; Zhang, X.; Brewer, J. A.; Hameed, R.; Chai, J.; Lu, Y.; Ware, S. A.; Zhou, S.; Wen, Y.; Lalami, H.; Hossein Beigi, H.; Yuan, J.; Liao, J.; Hong, Y.; Wu, M.; Tong, D.; Sapkota, D.; Ding, Y.

doi:10.1101/2025.10.13.682248

bioRxiv · 10.1101/2025.10.13.682248

Axially swept dithered light-sheet microscope to reveal cardiac morphology

Almasian, M.·Saberigarakani, A.·Zhang, X.·Brewer, J. A.·Hameed, R.·Chai, J.·Lu, Y.·Ware, S. A.·Zhou, S.·Wen, Y.·Lalami, H.·Hossein Beigi, H.·Yuan, J.·Liao, J.·Hong, Y.·Wu, M.·Tong, D.·Sapkota, D.·Ding, Y.

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Abstract

Understanding cardiac microstructure and vascular networks in their entirety is critical for assessing cardiovascular development, disease progression, and therapeutic interventions. Light-sheet microscopy combined with tissue clearing enables high-resolution volumetric imaging of intact organs but faces limitations in trabeculated myocardium due to trade-offs among light-sheet thickness, effective range, and frame rate. We exploit temporal dynamics that govern illumination-detection interplay to maintain uniform resolution across specimens. Building on this, we implemented high-speed dithered light-sheet (DiLS) illumination, extending the confocal region by over 40% and enhancing the space-bandwidth product while preserving optical sectioning. Integration of DiLS with a sweeping approach establishes the axially swept dithered light-sheet (AS-DiLS), which enhances imaging throughput while preserving axial resolution and enables uniform illumination up to 12.5-millimeter range. AS-DiLS delivers near-isotropic resolution (~2.5 m) for investigating intricate ventricular trabeculae, vasculature, and extracellular matrix, providing a scalable platform for comprehensive cardiovascular morphology and topology assessment from embryos to adults. TeaserVolumetric imaging reveals microstructure and vascular networks in their entirety with near-isotropic resolution.

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Almasian, M., Saberigarakani, A., Zhang, X., Brewer, J. A., Hameed, R., Chai, J., Lu, Y., Ware, S. A., Zhou, S., Wen, Y., Lalami, H., Hossein Beigi, H., Yuan, J., Liao, J., Hong, Y., Wu, M., Tong, D., Sapkota, D., Ding, Y.. 2025-10-15. Axially swept dithered light-sheet microscope to reveal cardiac morphology. https://doi.org/10.1101/2025.10.13.682248

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