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Deep-brain fluorescence imaging

深部脑荧光成像

基本信息

批准号：
BB/P02730X/1
负责人：
N Emptage
金额：
$ 19.22万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP02730X%2F1
关键词：
Deep brain fluorescence imaging

项目摘要

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.

我们对大脑的许多了解，我们之所以知道，是因为我们可以用显微镜对其成像。我们可以观察每个神经元内部的微小特征，看看它是如何构建的，或者通过使用当大脑的各个部分工作时都会发光的染料来观察电活动。不幸的是，这意味着我们对大脑表面的了解远远超过对深埋其中的部分的了解，只是因为我们不能将大型显微镜挤进这么小的空间。为了真正了解大脑，我们必须找到一种方法来对埋藏的部分进行成像。将显微镜放入大脑内部是困难的，因为透镜很大。此前，人们曾尝试使用微型显微镜成像，但尽管使用这些显微镜可以很快获得图像，但它们很笨重，插入时会对大脑造成相当大的损害。光纤可以获得相同的图像，但直径要小得多，这意味着损害更小。可以理解的是，如果我们造成了太多的损害，我们不能再确定我们在大脑中观察到的东西是否反映了它在自然状态下的行为；这种情况在很大程度上是当今高分辨率深部脑成像的现状。不幸的是，沿着光纤传输的光被扰乱了。这个项目专注于寻找一种方法来解读它，使用全息图--将图像中的所有信息编码的光图案，而不是人们在2D照片中看到的仅仅是其中的一部分。通过投射全息图而不是照片，我们可以预置光，补偿光纤的影响，并允许我们成像到大脑深处。我们将设计和制造一台机器，可以极快地制作全息图--每秒大约25000张。通过仔细控制它们，我们可以投射出看起来混乱的图像，但一旦它们沿着光纤传播，它们就会变成我们想要的光模式。我们想要制造的仪器基于一些数字投影仪中使用的相同类型的芯片，由非常快地来回切换的微小小镜子组成。这让它们可以将照射到它们身上的光延迟很小的量，当所有像素一起工作时，我们就可以解读通过光纤传输的光。此前，我们已经证明可以使用不同的技术来投影全息图，但这项技术非常缓慢。相比之下，这里描述的新技术可以像普通显微镜一样快地成像，这意味着我们可以看到大脑中更多的特征，特别是变化的东西，比如电活动。我们将开发的全息投影仪还可以用于许多其他应用-3D打印、全息电视，以及通过打开和关闭神经元来控制老鼠的大脑。这很重要，因为它的速度大约是其他可以做类似事情的设备的100倍，所以即使它在老鼠的大脑中不起作用，它在其他领域也会非常有用。