2025-08-26 新潟大学
(A)シースルー法と従来のオープンスカル法の比較。
(B)迅速かつ可逆的に頭蓋骨を透明化して脳内をライブイメージングできる。
(C)マウス頭蓋骨は高度に透明化される。
(D)頭蓋骨を広範囲に透明化して「ズームアウト・ズームイン」観察できる。
(E)様々な脳領域の数千個の神経細胞の活動をモニターし(左)神経間ネットワーク解析(右)をできる。
<関連情報>
- https://www.bri.niigata-u.ac.jp/research/result/002333.html
- https://www.bri.niigata-u.ac.jp/research/result/20250826result.pdf
- https://www.nature.com/articles/s41467-025-62836-1
SeeThrough:生体脳イメージングのための合理的に設計された頭蓋骨透明化技術 SeeThrough: a rationally designed skull clearing technique for in vivo brain imaging
Xinyi Liu,Motokazu Uchigashima,Ikumi Oomoto,Yoshihito Saito,Hitoshi Uchida,Shinya Oginezawa,Keiko Masuda,Daisuke Satoh,Manabu Abe,Kenji Sakimura,Yoshihiro Shimizu,Masanori Murayama,Kazuki Tainaka & Takayasu Mikuni
Nature Communications Published:26 August 2025
DOI:https://doi.org/10.1038/s41467-025-62836-1
Abstract
Light scattering in the skull limits optical access to the brain. Here we present SeeThrough, a skull-clearing technique that enables simple, high-resolution, and minimally-invasive brain imaging without skull removal. Through systematic screening of over 1600 chemicals, we rationally developed a refractive index-matching solution that combines water- and organic solvent-based components, achieving both high clearing efficiency and biocompatibility. The reagents exhibit minimal brain penetration, maintain tissue integrity, and avoid inflammatory responses. Notably, SeeThrough provides imaging sensitivity and contrast comparable to open-skull window imaging, while permitting minimally-invasive monitoring of brain border macrophages as well as blood and cerebrospinal fluid dynamics. Combined with two-photon imaging, SeeThrough enables spatially and temporally scalable imaging applications in the mouse brain, including ~400 µm deep imaging, one-month longitudinal imaging, and mesoscale, cellular-resolution monitoring of brain activity for network-level analysis. Thus, SeeThrough offers a broadly accessible platform for high-throughput, physiology-preserving imaging of the brain parenchyma and brain-skull interface.
