PT  - JOURNAL ARTICLE
AU  - Chunyu Fang
AU  - Tingting Chu
AU  - Tingting Yu
AU  - Yujie Huang
AU  - Yusha Li
AU  - Peng Wan
AU  - Dan Wang
AU  - Xuechun Wang
AU  - Wei Mei
AU  - Dan Zhu
AU  - Peng Fei
TI  - Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy
AID  - 10.1101/825901
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 825901
4099  - http://biorxiv.org/content/early/2019/10/31/825901.short
4100  - http://biorxiv.org/content/early/2019/10/31/825901.full
AB  - We here report on a compressed sensing-enabled Bessel light-sheet microscopy system able to achieve fast scalable mapping of entire organs at an isotropic subcellular resolution. A dual-side confocally-scanned Bessel light-sheet with a millimeter-to-centimeter tunable range was developed to illuminate regions-of-interest from a few cells to entire organs, providing uniform optical sectioning of deep tissues with 1-5 μm ultra-thin axial confinement. We also present a new computation pipeline termed content-aware compressed sensing (CACS), which can further improve the contrast and resolution of a 3D image based on a single input of its own, allowing satisfying spatial resolution with data acquisition shorten by two-orders of magnitude. Using this method, we can image any region-of-interest of a selected mouse brain at submicron isotropic resolution in seconds, after screening multiple whole brains in minutes, and then in toto reconstruct the digital whole brain (∼400 mm3) at a teravoxel scale with a short acquisition time of ∼15 minutes. We also demonstrate subcellular-resolution minute-timescale dual-color imaging of neuromuscular junctions in thick mouse muscles. Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole tissue, were enabled by our high-throughput high-resolution imaging method.