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Sarah Spitz

Publications and source records attributed to Sarah Spitz.

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Self-localized ultrafast pencil beam for volumetric multiphoton imaging

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 (MMF) and demonstrate its application in volumetric multiphoton imaging. We show that self-focusing in step-index MMFs, traditionally considered detrimental, can facilitate the formation of a nonlinear spatiotemporal localized state with a sidelobe-suppressed Bessel-like beam profile, exhibiting markedly improved stability and noise characteristics. By simply launching an overfilled on-axis Gaussian beam into a standard MMF, a high-quality ultrafast pencil beam can be generated through a self-localized process and readily integrated into an existing multiphoton point-scanning microscope. We apply this self-localized pencil beam to two-photon imaging of intact mouse enteric nervous systems, benchmarking with diffraction-limited Gaussian beams and outperforming conventional Bessel beams with reduced sidelobes and enhanced resilience to tissue-induced aberration. Finally, we monitor the transferrin uptake dynamics in a live human blood-brain barrier model by combining NAD(P)H-FAD-based metabolic phenotyping with minute-resolved 3D scans, revealing spatially and temporally resolved inter- and intra-cell heterogeneity. Our findings provide new insights into nonlinear dynamics of multidimensional optical systems and offer a promising approach for generating robust ultrafast pencil beams, enabling high-throughput 3D biosystem imaging to elucidate biological transport pathways and guide the design of therapeutics requiring cell-specific delivery.

physics.optics

Deep and Dynamic Metabolic and Structural Imaging in Living Tissues

Label-free imaging through two-photon autofluorescence (2PAF) of NAD(P)H allows for non-destructive and high-resolution visualization of cellular activities in living systems. However, its application to thick tissues and organoids has been restricted by its limited penetration depth within 300 $\mu$m, largely due to tissue scattering at the typical excitation wavelength (~750 nm) required for NAD(P)H. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to over 700 $\mu$m in living engineered human multicellular microtissues by adopting multimode fiber (MMF)-based low-repetition-rate high-peak-power three-photon (3P) excitation of NAD(P)H at 1100 nm. This is achieved by having over 0.5 MW peak power at the band of 1100$\pm$25 nm through adaptively modulating multimodal nonlinear pulse propagation with a compact fiber shaper. Moreover, the 8-fold increase in pulse energy at 1100 nm enables faster imaging of monocyte behaviors in the living multicellular models. These results represent a significant advance for deep and dynamic metabolic and structural imaging of intact living biosystems. The modular design (MMF with a slip-on fiber shaper) is anticipated to allow wide adoption of this methodology for demanding in vivo and in vitro imaging applications, including cancer research, autoimmune diseases, and tissue engineering.

physics.optics