New type of microscope allows you to see the brain through the intact skull

Non-invasive microscopic techniques, such as optical coherence and two-photon microscopy, usually

are used for in vivo imaging of living tissues. When light passes through biological tissues, two types of light are generated: ballistic and multi-scattered photons.

Ballistic photons pass right throughobject, no deviation. They are used to restore the image of an object. In turn, multiple scattered photons are generated by random deflections as light passes through the material. As a result, they appear as grainy noise in the image. As the light travels further, the difference between scattered and ballistic photons increases, thus obscuring the information about the image.

Bone tissue has many complex internalstructures. They cause strong multiple scattering of light and complex optical aberrations. When it is necessary to obtain an optical image of the mouse brain through the intact skull, the fine structures of the nervous system are difficult to visualize. Grainy noise and other picture distortions interfere. This is a major obstacle in neurobiological research, where mice are often used as models. Because of such limitations in imaging techniques, the skull of mice must be removed or thinned out in order to examine the neural networks of the brain tissue beneath it.

A group of researchers led by a professorChoi Wonshika of the Center for Molecular Spectroscopy and Dynamics of the Institute for Basic Sciences (IBS) in Seoul, South Korea has made a major breakthrough in deep tissue optical imaging. They have developed a new optical microscope that can capture images through the intact skull of a mouse. As a result, scientists have access to a microscopic map of neural networks in brain tissues without loss of spatial resolution.

Schematic of a reflective matrix microscope developed by researchers at the IBS Center for Molecular Spectroscopy and Dynamics. Credit: IBS

The new reflective matrix microscope combinesin itself the capabilities of both hardware and computational adaptive optics (AO). This technology was originally developed for terrestrial astronomy to correct optical aberrations. A conventional confocal microscope measures the reflection signal only at the focal point of the illumination and rejects all non-focal light.

New reflective array microscoperegisters all scattered photons at positions other than the focal point. The scattered photons are then corrected by calculations using the new CLASS (Closed Single Scatter Accumulation) algorithm. This AO algorithm uses all of the scattered light to selectively extract ballistic light and correct optical aberrations.

The reflective matrix microscope has the great advantage that it can be directly combined with a conventional two-photon microscope, which is already widely used in the life sciences.

Our microscope allows you to explore the delicate internal structures deep in living tissues. This will greatly help in the early diagnosis of diseases and accelerate research in neuroscience.

Research Professor Yoon Sokchan

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