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

 描述(由申请人提供)：显微镜技术在脑组织内部成像通常受到深度穿透性差的限制。在显微内窥镜检查中，探针被物理地插入组织中，可以克服这种深度穿透的限制，但代价是由于探针的大小而造成侵入性和组织损伤。我们的目标是通过开发一种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。由于空间信息在传播时变得混乱，通过光纤fi直接传输图像是一种迷信(difficult)。我们最近展示了一种图像传输策略，其中空间信息被fiRst转换为光谱信息。我们的策略基于从无线通信中借用的扩频编码原理，其中对象像素被转换为跨越对象频谱的整个带宽的不同频谱代码。通过在fiBER输出处对检测到的光谱进行数值反转来执行图像恢复。我们已经提供了一个使用宏观法布里-珀罗标准具进行扩频编码的简单演示。我们的技术使发光(即荧光或生物发光)对象的2D成像具有与像素数无关的高通量。此外，它对fi波纹弯曲不敏感，不包含活动部件，并开启了极具吸引力的小型化可能性，最小到单个尺寸。 光纤。我们的目标是开发、表征和建立一种新型超小型光纤探头的多功能性，这种探头可以在任意深度提供功能性2D脑成像，并将组织损伤降至最低。我们的战略将包括探针开发、机器学习算法开发，以及在自由活动的行为动物中实际演示显微内窥镜成像。

 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.