Through-skull brain imaging in vivo at visible wavelengths via dimensionality reduction adaptive-optical microscopy

• Published in: Science advances 2022-07, Vol.8 (30), p.eabo4366-eabo4366
• Main Authors: Jo, Yonghyeon, Lee, Ye-Ryoung, Hong, Jin Hee, Kim, Dong-Young, Kwon, Junhwan, Choi, Myunghwan, Kim, Moonseok, Choi, Wonshik
• Format: Article
• Language: English
• Subjects: Applied Physics; Optics; Physical and Materials Sciences; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abo4366

Compensation of sample-induced optical aberrations is crucial for visualizing microscopic structures deep within biological tissues. However, strong multiple scattering poses a fundamental limitation for identifying and correcting the tissue-induced aberrations. Here, we introduce a label-free deep-tissue imaging technique termed dimensionality reduction adaptive-optical microscopy (DReAM) to selectively attenuate multiple scattering. We established a theoretical framework in which dimensionality reduction of a time-gated reflection matrix can attenuate uncorrelated multiple scattering while retaining a single-scattering signal with a strong wave correlation, irrespective of sample-induced aberrations. We performed mouse brain imaging in vivo through the intact skull with the probe beam at visible wavelengths. Despite the strong scattering and aberrations, DReAM offered a 17-fold enhancement of single scattering–to–multiple scattering ratio and provided high-contrast images of neural fibers in the brain cortex with the diffraction-limited spatial resolution of 412 nanometers and a 33-fold enhanced Strehl ratio. Deep imaging based on wave correlation is used to attenuate multiple scattering and visualize mice brains through intact skulls.