High numerical aperture confocal volumetric mesoscope reveals mesoscale subcellular dynamics in vivo.

Authors

Zhi Lu, Minghuan Wang, Wentao Chen, Manchang Jin, Laiyu Zhu, Tianyun Wang, Qi Zhang, Yi Yang, Chaowei Zhuang, Jiamin Wu, Wei Wang, Qionghai Dai

Published in

Nature biotechnology. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Simultaneously capturing subcellular dynamics across thousands of cells in mammals remains challenging because of trade-offs among spatial resolution, field of view, imaging speed and sample viability, particularly under high-NA (numerical aperture) conditions. Here we design a high-NA mesoscale objective lens and present a confocal volumetric mesoscope with an NA of 1.05, RUSH3D-HR, achieving ~390-nm resolution across a volume of 2.7 × 2.0 × 0.04 mm³ at five volumes per second with low phototoxicity. By integrating our previously developed confocal scanning light-field framework with a parallelized deep-learning pipeline, RUSH3D-HR increases experimental efficiency by orders of magnitude. Long-term imaging at 70 billion voxels per second visualizes immune responses such as long-distance collective cell migrations during wound healing and large-scale migrasome generation and neutrophil-macrophage interactions during acute liver failure. Hour-long monitoring over 6,000 neutrophils reveals transient emergent swarming behaviors in mouse spleen during lipopolysaccharide-induced inflammation, which is suppressed with electroacupuncture at ST36, providing direct evidence for the immunomodulatory mechanism of peripheral electrical stimulation.

PMID:
42458054
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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