In vivo deep-brain microscopy at submicrometer resolution with refractive index-matched prism interfaces

Takahashi, T.; Zhou, Y.; Tsutsumi, M.; Ito, C.; Hatakeyama, A.; Ishii, H.; Saitoh, A.; Yukawa, H.; Nabekura, J.; Nemoto, T.; Otomo, K.; Matsuhisa, N.; Agetsuma, M.

doi:10.1101/2025.05.30.657010

bioRxiv · 10.1101/2025.05.30.657010

In vivo deep-brain microscopy at submicrometer resolution with refractive index-matched prism interfaces

Takahashi, T.·Zhou, Y.·Tsutsumi, M.·Ito, C.·Hatakeyama, A.·Ishii, H.·Saitoh, A.·Yukawa, H.·Nabekura, J.·Nemoto, T.·Otomo, K.·Matsuhisa, N.·Agetsuma, M.

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Abstract

The mammalian brain is a thick and densely layered structure comprising a huge number of neurons that work together to process information and regulate brain functions. Although various optical methods have been developed to investigate deep brain dynamics, they are limited by technical constraints, invasiveness, suboptimal spatial resolution, and/or a restricted field of view. To overcome these limitations, we developed an implantable, optically optimized microprism interface with a refractive index matched to that of brain tissue and water, enabling minimally-invasive, wide-field two-photon imaging method with enhanced brightness and sub-micron resolution in deep prefrontal areas.

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Takahashi, T., Zhou, Y., Tsutsumi, M., Ito, C., Hatakeyama, A., Ishii, H., Saitoh, A., Yukawa, H., Nabekura, J., Nemoto, T., Otomo, K., Matsuhisa, N., Agetsuma, M.. 2025-06-02. In vivo deep-brain microscopy at submicrometer resolution with refractive index-matched prism interfaces. https://doi.org/10.1101/2025.05.30.657010

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