Deep-brain fluorescence imaging

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Much of what we know about the brain, we know because we can image it using a microscope. We can look at the tiny features inside each neuron to see how it is built, or look at the electrical activity by using dyes which glow whenever parts of the brain are working. Unfortunately, this means that we know much more about the surface of the brain than we do about the parts buried deep within, just because we can't squeeze a large microscope into such a small space. To truly understand the brain, we must find a way to image the buried parts too.Putting a microscope inside the brain is hard, because lenses are big. Previously, people have tried to image using tiny microscopes, but while it is possible to get an image quite quickly using these microscopes, they are bulky and do considerable damage to the brain as they are inserted. An optical fiber can get the same image, but with a much smaller diameter, which means less damage. Understandably, if we cause too much damage, we can no longer be certain that what we observe in the brain reflects how it acts in its natural state; a situation which is largely the current state of high-resolution deep brain imaging today.Unfortunately, the light that travels along an optical fiber is scrambled. This project is focused on finding a way to unscramble it, using holograms - patterns of light that encode all the information in an image, rather than just part of it as one would see in a 2D photograph. By projecting a hologram instead of a photograph, we can 'pre-scramble' the light, compensating for the effect of the fiber and allowing us to image deep inside the brain. We will design and build a machine that can make holograms extremely quickly - around 25 thousand of them per second. By carefully controlling them, we can project images that appear scrambled, but once they travel down the optical fiber, they turn into the pattern of light that we want.The instrument we would like to make is based on the same type of chip that is used in some digital projectors, consisting of tiny little mirrors that flip back and forth very rapidly. This lets them delay the light hitting them by a very small amount, which when all the pixels operate together, allows us to unscramble the light travelling through the optical fiber. Previously, we have shown that we can project holograms using a different technology, but this technology is very slow. In contrast, the new technique described here can image just as fast as a normal microscope, which means we can see more features in the brain, especially things that change, like electrical activity.The holographic projector we will develop is useful for many other applications - 3D printing, holographic TV, as well as controlling a mouse brain by switching neurons on and off. It is important because it is approximately one hundred times faster than other devices that can do similar things, so even if it doesn't work in the mouse brain, it will be very useful in other areas.