Abstract

Intravital microscopy (IVM) offers the opportunity to visualize static and dynamic changes of tissue on a cellular level. It is a valuable tool in research and may considerably improve clinical diagnosis. In contrast to confocal and non-linear microscopy, optical coherence tomography (OCT) with microscopic resolution (mOCT) provides intrinsically cross-sectional imaging. Changing focus position is not needed, which simplifies especially endoscopic imaging. For in-vivo imaging, here we are presenting endo-microscopic OCT (emOCT). A graded-index-lens (GRIN) based 2.75 mm outer diameter rigid endoscope is providing 1.5 - 2 µm nearly isotropic resolution over an extended field of depth. Spherical and chromatic aberrations are used to elongate the focus length. Simulation of the OCT image formation, suggests a better overall image quality in this range compared to a focused Gaussian beam. Total imaging depth at a reduced sensitivity and lateral resolution is more than 200 µm. Using a frame rate of 80 Hz cross-sectional images of concha nasalis were demonstrated in humans, which could resolve cilial motion, cellular structures of the epithelium, vessels and blood cells. Mucus transport velocity was successfully determined. The endoscope may be used for diagnosis and treatment control of different lung diseases like cystic fibrosis or primary ciliary dyskinesia, which manifest already at the nasal mucosa.

Highlights

  • Histology of excised tissue is the state-of-the-art diagnostic tool for a large number of major diseases like tumors, inflammatory or metabolic disorders

  • The endoscope may be used for diagnosis and treatment control of different lung diseases like cystic fibrosis or primary ciliary dyskinesia, which manifest already at the nasal mucosa

  • The Rayleigh length of this Gaussian beam would be below 4.5 μm and the Full width at half maximum (FWHM) of the beam would degrade from 1.25 μm to less than 2 μm within 7 μm

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Summary

Introduction

Histology of excised tissue is the state-of-the-art diagnostic tool for a large number of major diseases like tumors, inflammatory or metabolic disorders. Beside invasiveness for obtaining the tissue sample, a major drawback of classical histology is, that it provides information only for one time point. Intravital microscopy (IVM) offers the opportunity to image the dynamics of disease related tissue changes. The examination of tissues inside the body needs the combination of high-resolution imaging with endoscopy. Laser scanning endo-microscopy was demonstrated for imaging small and large intestine [7,8,9] and other tissues [10]. Only morphologic changes of a single cell layer are directly visualized and in vivo histological like cross-sectional imaging gets very challenging and time consuming due to the missing depth information

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