Joint study develops STABLE endoscopy

Recently, a joint team from the Zhejiang University College of Optical Science and Engineering and Zhejiang Lab, led by Professors LIU Xu and YANG Qing, developed a technique called “spatial-frequency tracking adaptive beacon light-field encoding” (STABLE) for achieving super-resolution imaging (λ/3NA) based on multimode fibers (MMFs). Stable transmission and reconstruction of light fields in complex media (dynamic optical fibers, clouds, fog, turbid liquids, etc.) pose common challenges in imaging and optical communication fields. This study provides a universal method to address this problem, taking a substantial step towards the practical application of MMF-based endoscopy in life sciences, biology, industrial inspection, and clinical diagnosis. The findings were published in an open-access article entitled “Single multimode fiber for in vivo light-field-encoded endoscopic imaging” in the journal Nature Photonics on July 3.

One of the ultimate dreams of endoscopists would be an ultrathin real-time high-resolution endoscopy that combines in vivo imaging and therapeutic intervention, resulting in an endoscopic diagnosis that matches an in vitro pathological diagnosis. Considerable progress has been made in endoscopy in recent years. Endocytoscopy, confocal laser endomicroscopy and other techniques have been developed to make in vivo cellular imaging a reality. Meanwhile, super-resolution microscopy, surpassing subcellular spatial resolution, has led to revolutionary breakthroughs in the fields of biology and life sciences. However, the application of super-resolution microscopy in narrow channels, especially for an ultra-thin fiber, about 0.2mm in diameter, faces challenges due to complex optical setups. In fact, one critical missing technology is to achieve robust in vivo nano-endoscopy. One promising strategy is to employ thin MMFs (micrometers in scale) as minimally invasive probes using wavefront shaping. Compared to traditional endoscopy, MMF-based endoscopy is featured by slenderness, high-resolution, and low-cost. However, this technology has two key limitations: the operational inflexibility due to the strong movement dependence on the fiber’s configuration and the diffraction-limited resolution due to limited numerical aperture (NA).

Based on their previous research in fiber bundle confocal endoscopy, endocytoscopy, and frequency-shifted super-resolution modulation imaging, LIU Xu and YANG Qing et al. proposed STABLE endoscopy. By taking advantage of the cylindrically symmetric waveguide of MMFs and such multidisciplinary technologies as dimensionality reduction single-pixel tracking and dual feedback loops, they improved the tracking speed from several minutes to milliseconds, thus addressing the global challenge of imaging disturbances caused by unstable MMFs during motion. This allowed them to achieve lens-free super-resolution dynamic imaging over the longest distance in the world using a single multimode optical fiber.

In STABLE endoscopy, the team designed a full-vector modulation (FVM) incident wavefront that focuses the distal-end Fresnel reflection light on a single-pixel detector in the spatial frequency domain (the Fourier plane of the proximal facet of the fiber), forming a spatial-frequency beacon. The beacon transfers from spatial speckle tracking to single-pixel spatial-frequency beacon tracking. Its intensity reflects the correlation between the current bending state and the pre-calibrated transmission matric. By analyzing the simulation of light propagation in the fiber and the relationship between the reflection light and the spatial-frequency beacon, the team found that the intensity detected by the single-pixel detector is directly related to the chaotic phase, polarization, and amplitude caused by fiber deformation. Leveraging the radial cylindrically symmetric waveguide of the MMF, they introduced dimensionality reduction single-pixel tracking, significantly compressing the complexity of the state search problem to a much lower order. It was therefore possible to search for the correct transmission matrix under deformation by tracking the beacon.

For clinical analysis, it is necessary to locate the target area in complex scenes. To bridge the gap between macroscopic and microscopic morphologies, wide field-of-view and high-resolution 3D imaging capabilities must be combined. By placing the MMF in the biopsy channel of white-light endoscopy, they integrated STABLE with their independently developed white-light endoscope. Thanks to wide field-of-view navigation, they achieved 3D imaging and super-resolution imaging.

Using the STABLE endoscope guided by white-light endoscopy, the team is the first to achieve high-resolution in vivo imaging of the mouse esophagus, colon, gastrointestinal tract, subcutaneous intestine cancer, and small intestine.

This study involves the cross-disciplinary integration of optics, informatics, materials, physics, and medicine, thus making MMF-based imaging inside narrow lumens or solid organ tissues more reliable and accurate and laying a solid foundation for subsequent studies in clinical science, medicine, and precision industrial inspection.