A novel holographic microscope could image mouse brain through its skull

More than 80 times the light energy

In particular, the researchers developed a method for preferentially selecting simply scattered waves by taking advantage of the fact that they have similar reflection waveforms even when light is incident from different angles.

By using a complex algorithm and numerical operation that analyzes a medium’s eigenmode (a unique wave that delivers light energy into a medium), a resonance mode can be found that maximizes constructive interference (interference that occurs when waves superimposed on the same phase). ) between light wavefronts, this novel microscope focuses more than 80 times the light energy on the nerve fibers than before, while selectively removing unnecessary signals.

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“When we first observed the optical resonance of complex media, our work attracted a great deal of scientific attention,” said Professor Kim Moonseok and Dr. JO Yonghyeon who developed the fundamentals of the holographic microscope.

“From the basic principles to the practical application of observing the neural network under the mouse skull, we have opened a new path for the convergent technology of brain neuroimaging by combining the efforts of talented people in physics, life sciences and brain sciences.”

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Compensating for 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 present a label-free deep-tissue imaging technique, termed adaptive optical microscopy for dimension reduction (DReAM), to selectively mitigate multiple scattering. We have established a theoretical framework in which dimensionality reduction of a timed reflection matrix can attenuate uncorrelated multiple scattering while preserving a single scattering signal with strong wave correlation, independent of sample-induced aberrations. We performed in vivo imaging of the mouse brain through the intact skull with the probe beam at visible wavelengths. Despite the strong scattering and aberrations, DReAM offered a 17-fold improvement in the single scatter to multiple scatter ratio and provided high-contrast images of nerve fibers in the cerebral cortex with the diffraction-limited spatial resolution of 412 nanometers and a 33-fold improved Strehl ratio.

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