A new microscope allows scientists to see the skull and image the brain

Compensation for sample-generated optical aberrations is critical for visualizing microstructures in the depths of biological tissues. However, strong multiple scattering limits the ability to detect and repair tissue-induced errors.

Therefore, to obtain a high-resolution deep tissue image, it is necessary to remove multiple scattered waves and increase the proportion of single scattered waves. The scientists, led by Associate Director CHOI Wonshik of the Center for Molecular Spectroscopy and Dynamics within the Institute of Basic Sciences, Professor Kim Munseok of the Catholic University of Korea, and Professor CHOI Myunghwan of Seoul National University have developed a new type of holographic microscope, see through the skull and image brain.

The new microscope can achieve ‘see-through’ a healthy skull and is capable of high-resolution 3D imaging of the neural network inside the brain of a living mouse without removing the skull.

In 2019, scientists from Irritable Bowel SyndromeFor the first time, it has developed a high-speed, time-analyzing holographic microscope that can eliminate polydispersion. At the same time, it measures the amplitude and phase of light.

Using a microscope, they can observe the neural network of live fish without invasive surgery. However, it was difficult to obtain an image of the neural network of the rat brain because the rat’s skull is thicker than the fish’s.

The study team was able to quantitatively analyze how light and matter interact, allowing them to develop their previous microscope further. This recent study reports the successful development of an ultra-deep, three-dimensional, time-resolved microscope that allows the observation of tissues at ever greater depth.

Scientists, specifically, have developed a way to preferentially select scattered waves by taking advantage of the fact that they have similar reflective waveforms even when light is introduced from different angles.

To find out the resonance mode that improves constructive interference (interference that occurs when waves of the same phase overlap), a complex algorithm and numerical process are used that examines the intrinsic mode of the medium (a characteristic wave that distributes light energy in a medium). This allowed the new microscope to selectively filter out unwanted signals while focusing more than 80 times as much light energy on brain fibers as before. This made it possible to increase the ratio of scattered single waves to scattered waves by several orders of magnitude.

The scientists then tested the technology by observing the mouse’s brain. Even at depths where the use of current technology was previously impossible, wavefront distortion can be corrected with a microscope. The new microscope has succeeded in imaging the neural network of the mouse brain under the skull with high resolution. All of this was achieved at visible wavelength without removing the mouse skull and without using a fluorescent marker.

Professor Kim Munseok and Dr. Joo Yeon-yeon, who developed the basis for the holographic microscope, said, When we first observed the optical resonance of complex media, our work received a lot of attention from academia. From basic principles to the practical application of observing the neural network beneath the mouse’s skull, we’ve unlocked a new approach to converging technology for brain neuroimaging by combining the efforts of people talented in physics, life and brain Sciences.”

Associate Director CHOI Wonshik said, “For a long time, our center has developed a super-deep bio-imaging technology that applies physical principles. Our current findings are expected to contribute significantly to the development of multidisciplinary biomedical research, including neuroscience and the microscale industry.”

Journal reference:

  1. Yonghyeon Jo, Ye-Ryoung Lee, Jin Hee Hong, Dong-Young Kim, Junhwan Kwon, Myunghwan Choi, Moonseok Kim, and Wonshik Choi. Transcranial brain imaging in vivo at visible wavelengths by dimensional adaptive optical microscopy. science progress, 2022; 8 (30) DOI: 10.1126 / sciadv.abo4366