Deep-brain fluorescence imaging

我们对大脑的大部分了解都是因为我们可以使用显微镜对其进行成像。我们可以通过观察每个神经元内部的微小特征来了解它是如何构建的，或者通过使用大脑部分工作时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比我们对深埋在里面的部分的了解要多得多，只是因为我们不能把一个大型显微镜塞进这么小的空间。为了真正了解大脑，我们必须找到一种方法来成像隐藏的部分。把显微镜放在大脑内部是很困难的，因为镜头很大。以前，人们曾尝试使用微型显微镜进行成像，但虽然使用这些显微镜可以快速获得图像，但它们体积庞大，并且在插入时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，这意味着损坏更少。可以理解的是，如果我们造成了太多的损伤，我们就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脑深部成像的现状。不幸的是，光在沿着光纤传播时是混乱的。这个项目的重点是找到一种方法来解读它，使用全息图-光的模式，编码在图像中的所有信息，而不是只是它的一部分，因为人们会看到一个2D照片。通过投影全息图而不是照片，我们可以“预先扰乱”光线，补偿光纤的影响，使我们能够在大脑深处成像。我们将设计和建造一台机器，它可以非常快地制作全息图-每秒大约25000张。通过仔细控制它们，我们可以投射出看起来杂乱的图像，但是一旦它们沿着光纤传播，它们就会变成我们想要的光的图案。我们想要制造的仪器是基于与某些数字投影仪相同类型的芯片，由非常快速地来回翻转的微小镜子组成。这使得它们可以将到达它们的光延迟一个非常小的量，当所有的像素一起工作时，可以让我们解读通过光纤的光。以前，我们已经证明，我们可以使用不同的技术投影全息图，但这种技术非常慢。相比之下，这里描述的新技术可以像普通显微镜一样快速成像，这意味着我们可以看到大脑中更多的特征，特别是那些变化的东西，比如电活动。我们将开发的全息投影仪可以用于许多其他应用- 3D打印，全息电视，以及通过开关神经元来控制老鼠大脑。这很重要，因为它比其他可以做类似事情的设备快大约一百倍，所以即使它在老鼠大脑中不起作用，它在其他领域也会非常有用。

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.