Abstract

Flexible endomicroscopes commonly use coherent fiber bundles with high core densities to facilitate high-resolution in vivo imaging during endoscopic and minimally-invasive procedures. However, under-sampling due to the inter-core spacing limits the spatial resolution, making it difficult to resolve smaller cellular features. Here, we report a compact and rapid piezoelectric transducer (PZT) based bundle-shifting endomicroscopy system in which a super-resolution (SR) image is restored from multiple pixelation-limited images by computational means. A miniaturized PZT tube actuates the fiber bundle behind a GRIN micro-lens and a Delaunay triangulation based algorithm reconstructs an enhanced SR image. To enable real-time cellular-level imaging, imaging is performed using a line-scan confocal laser endomicroscope system with a raw frame rate of 120 fps, delivering up to 2 times spatial resolution improvement for a field of view of 350 µm at a net frame rate of 30 fps. The resolution enhancement is confirmed using resolution phantoms and ex vivo fluorescence endomicroscopy imaging of human breast specimens is demonstrated.

Highlights

  • The ability to analyse tissue morphology in its natural biological environment, without excising a sample for pathology, could significantly impact the diagnosis and treatment of a range of diseases

  • Several configurations for fiber optic confocal endomicroscopes have been developed in the past

  • Using the Sparrow criterion the required shift is about 2.12 μm. If we compare these values to the core spacing of 4.48 μm, it is clear that there is significant under-sampling occurring in conventional fiber bundle systems, and a potential for up to a 2-fold resolution improvement by fiber shifting

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Summary

Introduction

The ability to analyse tissue morphology in its natural biological environment, without excising a sample for pathology, could significantly impact the diagnosis and treatment of a range of diseases Thin coherent waveguides such as optical fibers and fiber bundles have played a key role in bridging the gap between microscopes and endoscopes, providing a route to non-invasive cellular-level visualization and assessment of human tissue in-vivo and in real-time [1]. They broadly fall into two categories: (i) distal scanning mechanisms using MEMS or piezo elements [6, 11, 12], and (ii) proximal scanning systems using bare fiber bundles or fiber bundles with distal optics [4, 5] The former typically use a single optical fiber for light delivery and collection. The typically large diameter of the distal tip (∼ 5 mm) and often low scanning rates (∼ 1 frame/second) greatly restricts their applicability for real-time clinical imaging applications

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