Scientists have developed a new type of microscope that is able to see through skulls.
A research team led by professor Choi Wonshik at the Centre for Molecular Spectroscopy and Dynamics in Seoul developed the tool, which has been able to create a microscopic map of neural networks in a mouse’s brain through the animal’s skull.
Such an act is difficult to achieve without damaging flesh and bone. Skulls are thick, and inconsistent, which means that light shone on them scatters easily. The deeper that scientists wish to see, the more difficult it becomes.
Even when it is achievable, it is challenging. When light travels through biological tissue, two types of photons (the massless elementary particle that makes up light) are generated: ballistic photons and multiply scattered photons.
Ballistic photons can travel straight through the object without deflection, but the scattered photons show up as noise on the image. The further through the light has to travel, the worse this ratio becomes, as scattered photons become more numerous than ballistic photons.
Moreover, optical aberration of ballistic photons can reduce the contrast and blur the image when the picture is reconstructed. In neuroscience research, this has meant that optical imaging a mouse’s brain has meant the skull has to be removed or thinned.
This new microscope, however, might provide the answer. Called a reflection matrix microscope, it uses both its own hardware and a computational adaptive optics algorithm to correct faults in the image.
Conventional imaging microscopes discard all out of focus light when they are used, only focusing on those at the point of illumination; this reflection matrix microscope, by contrast, records all the scattered photons at their positions.
The algorithm then corrects the scattered photons, selectively extracts ballistic light, and corrects severe optical aberrations. The scientists claim that the number of aberrations that can be corrected is 10 times greater than that of standard systems.
“Reflection matrix microscope is the next-generation technology that goes beyond the limitations of conventional optical microscopes,” professor Choi said.
“This will allow us to widen our understanding of the light propagation through scattering media and expand the scope of applications that an optical microscope can explore.”
This microscope also has the advantage of being able to be used in conjunction with conventional two-photon microscopes that are being used in life sciences, removing aberrations in the image.
The team demonstrated this by taking a florescent images of a dendritic spine of a neuron behind a mouse’s skill – something that would not normally be possible without removing brain tissue entirely.
This new development means it is now possible to investigate the brain in its most native states, the scientists claim.
“By correcting the wavefront distortion, we can focus light energy on the desired location inside the living tissue”, said professor Yoon Seokchan and graduate student Lee Hojun, who conducted the study, in a statement.
“Our microscope allows us to investigate fine internal structures deep within living tissues that cannot be resolved by any other means. This will greatly aid us in early disease diagnosis and expedite neuroscience research.”
The research, entitled “Laser scanning reflection-matrix microscopy for aberration-free imaging through intact mouse skull”, was published in Nature Communications.