Abstract

Optical imaging techniques using a variety of contrast mechanisms are under evaluation for early detection of epithelial precancer; however, tradeoffs in field of view (FOV) and resolution may limit their application. Therefore, we present a multiscale multimodal optical imaging system combining macroscopic biochemical imaging of fluorescence lifetime imaging (FLIM) with subcellular morphologic imaging of reflectance confocal microscopy (RCM). The FLIM module images a 16×16 mm² tissue area with 62.5 μm lateral and 320 ps temporal resolution to guide cellular imaging of suspicious regions. Subsequently, coregistered RCM images are acquired at 7 Hz with 400 μm diameter FOV, <1 μm lateral and 3.5 μm axial resolution. FLIM-RCM imaging was performed on a tissue phantom, normal porcine buccal mucosa, and a hamster cheek pouch model of oral carcinogenesis. While FLIM is sensitive to biochemical and macroscopic architectural changes in tissue, RCM provides images of cell nuclear morphology, all key indicators of precancer progression.

Highlights

  • Eighty to ninety percent of all cancers originate in epithelial tissues, such as in the oral cavity, cervix, esophagus, and colon.[1]

  • We present a dual modality imaging system to detect both biochemical and morphological changes that are associated with oral precancer progression

  • The reflectance confocal microscopy (RCM)-fluorescence lifetime imaging (FLIM) system was first characterized by imaging fluorescent and reflective United States Air Force (USAF) resolution targets

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Summary

Introduction

Eighty to ninety percent of all cancers originate in epithelial tissues, such as in the oral cavity, cervix, esophagus, and colon.[1]. The ideal optical diagnostic would have high sensitivity macroscopic surveillance guiding high resolution and high specificity imaging for diagnosis

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