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

Scientists have invented a new type of the microscope that allows you to see biological tissue through an intact skull. It uses a combination of hardware and software adaptive optics to reconstruct an object’s image.

Non-invasive microscopic techniques such as optical coherence and two-photon microscopy are commonly used to visualize living tissue in vivo. When light passes through biological tissues, two light types are generated: ballistic photons and multiply scattered photons.

Ballistic photons pass directly through the object without deflection. They are used to restore the image of an object. In turn, multiply 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 image’s information.

Bone tissue has many complex internal structures. 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 an intact skull, the nervous system’s fine structures are difficult to visualize. Grainy noise and other picture distortions interfere. This is a major hurdle in neurobiological research, where mice are often used as models. Because of such limitations in imaging techniques, mice’s skull must be removed or thinned out to examine the neural networks of the brain tissue beneath it.

A team of researchers led by Professor Choi Wonshik of the Center for Molecular Spectroscopy and Dynamics of the Institute for Basic Sciences (IBS) in Seoul, South Korea, has made a 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 spatial resolution loss.

The new microscope is a reflective matrix and combines both hardware and computational adaptive optics (AO) capabilities. 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.

The new reflective array microscope records 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 the scattered light to extract ballistic light and correct optical aberrations selectively.

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 fine internal structures deep in living tissues. This will greatly help in the early diagnosis of diseases and accelerate neuroscience research.

Research Professor Yoon Sokchan

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