Ultra-miniaturized single fiber probe for functional brain imaging in freely moving animals

 描述（由申请人提供）：用于脑组织内部成像的显微镜技术通常受到深度穿透差的限制。其中探针物理插入组织中的显微内窥镜检查可以克服深度穿透的这种限制，但是由于探针的尺寸而以侵入性和组织损伤为代价。我们的目标是通过开发基于单根无透镜光纤的超微型显微内窥镜探头来缓解这些问题。 图像通过光纤的直接传输是困难的，因为空间信息在传播时变得混乱。我们最近展示了一种图像传输策略，其中空间信息首先转换为光谱信息。我们的策略是基于扩频编码的原理，借用无线通信，其中对象像素被转换成不同的频谱代码，跨越整个带宽的对象频谱。图像恢复是通过在光纤输出端检测到的光谱的数值反演来执行的。我们已经提供了一个简单的示范扩频编码使用宏观法布里-珀罗标准具。我们的技术使发光（即荧光或生物发光）对象的2D成像具有高吞吐量独立于像素数。此外，它对纤维弯曲不敏感，不包含移动部件，并打开了极小型化的可能性， 光纤 我们的目标是开发，表征和建立一类新的超微型光纤探头的多功能性，可以在任意深度提供功能性2D脑成像，并以最小的组织损伤。我们的策略将涉及探针开发，机器学习算法开发，以及在自由移动行为动物中进行显微内窥镜成像的实际演示。

 DESCRIPTION (provided by applicant): Microscope techniques to image inside brain tissue are generally limited by poor depth penetration. Micro-endoscopy, wherein a probe is physically inserted into the tissue, can overcome this limitation in depth penetration, but at the expense of invasiveness and tissue damage due to the size of the probe. Our goal here is to palliate these problems by developing an ultra-miniature microendoscope probe based on a single, lensless optical fiber. The direct transmission of an image through an optical fiber is difficult because spatial information becomes scrambled upon propagation. We have recently demonstrated an image transmission strategy where spatial information is first converted to spectral information. Our strategy is based on a principle of spread-spectrum encoding, borrowed from wireless communications, wherein object pixels are converted into distinct spectral codes that span the full bandwidth of the object spectrum. Image recovery is performed by numerical inversion of the detected spectrum at the fiber output. We have provided a simple demonstration of spread-spectrum encoding using macroscopic Fabry-Perot etalons. Our technique enables the 2D imaging of luminous (i.e. fluorescent or bioluminescent) objects with high throughput independent of pixel number. Moreover, it is insensitive to fiber bending, contains no moving parts, and opens the attractive possibility of extreme miniaturization down to the size of a single optical fiber. Our goal here is to develop, characterize, and establish the versatility of a new class of ultra-miniature fiber probes that can provide functional 2D brain imaging at arbitrary depths and with minimal tissue damage. Our strategy will involve probe development, machine-learning algorithm development, and the actual demonstration of microendoscopic imaging in freely moving behaving animals.