Self-localized ultrafast pencil beam for volumetric multiphoton imaging.

Cao, Honghao; Spitz, Sarah; Yu, Li-Yu; Liu, Kunzan; Zhang, Zhengyu; Presutti, Federico; Pramotton, Francesca Michela; Kulkarni, Subhash et al. · Nat Methods · 2026

basic_science · Level V

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Abstract

The formation of organized optical states in multidimensional systems is crucial for understanding light-matter interaction and advancing light-shaping technologies. Here we report the observation of a self-localized, ultrafast pencil beam near the critical power in a standard multimode fiber. We demonstrate that self-focusing, traditionally considered detrimental, facilitates a nonlinear spatiotemporal localized state with a sidelobe-suppressed Bessel-like profile and markedly improved stability. Generated simply by an on-axis Gaussian launch, this beam is readily integrated into standard multiphoton microscopes. We applied this self-localized beam to two-photon imaging of mouse enteric nervous systems, where it outperformed conventional Bessel beams through reduced sidelobes and enhanced aberration resilience. Lastly, we monitored transferrin uptake dynamics in a live human blood-brain barrier model using minute-resolved three-dimensional scans, revealing spatiotemporal heterogeneity across different cell types. Our findings offer a robust approach for generating ultrafast pencil beams, enabling high-throughput three-dimensional biosystem imaging to elucidate biological transport pathways.

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