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.

PUBLIC HEALTH RELEVANCE: We have recently demonstrated a strategy to image through a single, lensless optical fiber. We propose to develop this into an ultraminiaturized microendoscope for functional brain imaging with minimal surgical damage in freely moving behaving animals.