Confocal Airy beam oblique light-sheet tomography for brain-wide cell type distribution and morphology

Qi, Xiaoli, Muñoz-Castañeda, Rodrigo, Yue, Yuanlei, Xiao, Sheng, Ding, Liya, Narasimhan, Arun, Chen, Xin, Wang, Wei, Li, Yuanyuan, Elowsky, Corey, Palmer, Jason, Drewes, Rhonda, Sun, Jianjun, Wu, Jinglei, Qu, Lei, Wu, Zhuhao, Peng, Hanchuan, Osten, Pavel (November 2025) Confocal Airy beam oblique light-sheet tomography for brain-wide cell type distribution and morphology. Nature Methods. ISSN 1548-7091

Abstract

Advanced brain-wide mapping is critical for addressing complex questions in neuroscience. However, current imaging methods are limited by throughput, resolution and signal-to-noise ratio, constraining their broader applicability. Here, we present confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST): a system that integrates single-photon excitation with a scanned Airy beam light sheet, virtual slit detection and automated mechanical sectioning. CAB-OLST enables high-throughput, high-resolution and high-signal-to-noise ratio volumetric imaging, achieving an optical resolution of 0.77 μm × 0.49 μm × 2.61 μm. This allows for mouse brain-wide cell type distribution mapping at a voxel size of 0.37 μm × 0.37 μm × 1.77 μm in 10 h and single-neuron projectome imaging with a voxel size of 0.26 μm × 0.26 μm × 1.06 μm over 58 h. Compared to existing light-sheet and point-scanning systems, CAB-OLST provides a scalable and robust platform for comprehensive neuronal morphology reconstruction and high-precision cell atlas generation.

Item Type: Paper
Subjects: neurobiology
neurobiology > neuroscience
CSHL Authors:
Communities: CSHL labs > Mitra lab
CSHL labs > Osten lab
CSHL labs > Trotman lab
CSHL Post Doctoral Fellows
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 13 November 2025
Date Deposited: 17 Nov 2025 14:06
Last Modified: 17 Nov 2025 14:06
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42006

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