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

Yonghyeon Jo, Ye Ryoung Lee, Jin Hee Hong, Dong Young Kim, Junhwan Kwon, Myunghwan Choi, Moonseok Kim, Wonshik Choi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Article numbereabo4366
JournalScience Advances
Issue number30
Publication statusPublished - 2022 Jul

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health [grants T32MH020030 to M.J.L.; R01MH106595 to L.E.D., A.X.M., C.M.N.; R01HD059835 to B.G.; R01MH105379 to N.R.N.; R01MH108641 to N.R.N., and K02AA023239 to A.B.A.]. This work was funded by NIMH/U.S. Army Medical Research and Material Command [R01MH106595] and NIH 5U01MH109539. This work would have not been possible without the financial support provided by Stanley Center for Psychiatric Genetics at the Broad Institute, One Mind, and Cohen Veterans Bioscience.

Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.

ASJC Scopus subject areas

  • General


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