Abstract

In vivo endoscopic optical microscopy provides a tool to assess tissue architecture and morphology with contrast and resolution similar to that provided by standard histopathology – without need for physical tissue removal. In this article, we focus on optical imaging technologies that have the potential to dramatically improve the detection, prevention, and therapy of epithelial cancers. Epithelial pre-cancers and cancers are associated with a variety of morphologic, architectural, and molecular changes, which currently can be assessed only through invasive, painful biopsy. Optical imaging is ideally suited to detecting cancer-related alterations because it can detect biochemical and morphologic alterations with sub-cellular resolution throughout the entire epithelial thickness. Optical techniques can be implemented non-invasively, in real time, and at low cost to survey the tissue surface at risk. Our manuscript focuses primarily on modalities that currently are the most developed: reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). However, recent advances in fluorescence-based endoscopic microscopy also are reviewed briefly. We discuss the basic principles of these emerging technologies and their current and potential applications in early cancer detection. We also present research activities focused on development of exogenous contrast agents that can enhance the morphological features important for cancer detection and that have the potential to allow vital molecular imaging of cancer-related biomarkers. In conclusion, we discuss future improvements to the technology needed to develop robust clinical devices.

Highlights

  • In the developed world, cancer is the second leading cause of death, exceeded only by heart disease

  • We describe research activities focused on development of exogenous contrast agents that can enhance the morphological features important for cancer detection and can enable imaging of cancer-related molecular alterations

  • When low numerical aperture (NA) optics are combined with a 1300-nm broadband source and heterodyne detection allowed by modulation of the reference arm’s pathlength, optical coherence tomography (OCT) images can be obtained at depths of up to 2 mm [21]

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Summary

Introduction

Cancer is the second leading cause of death, exceeded only by heart disease. We review new developments in optical endoscopic microscopy that have the potential to improve the detection of these lesions. A number of promising new optical imaging technologies have emerged as potential tools for detecting pre-cancerous changes in vivo without the need for biopsy. We begin by discussing the basic principles of these emerging technologies and their current and potential applications in early cancer detection in the skin, cervix, esophagus, and oral cavity. Limitations of these technologies naturally lead to consideration of current research in disease markers that can be assessed using optical methods. We conclude by discussing future improvements needed to advance optical endoscopic microscopes to widespread clinical use for pre-cancer detection

Basic principles of RCM and OCT
Non-fiber-based reflectance confocal microscopy
Optical coherence tomography
Optical coherence microscopy
Confocal microscopy
Confocal reflectance microscopy
Optical coherence tomography and optical coherence microscopy
Current research in disease markers
Native sources of contrast
Contrast agents
Findings
Future improvements
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