Endomicroscope sheds light on cervical tissue

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Science Translational Medicine  11 Jan 2017:
Vol. 9, Issue 372, eaal4989
DOI: 10.1126/scitranslmed.aal4989


A pilot study of a handheld fluorescence endomicroscope demonstrates both in vivo imaging and differentiation of normal from precancerous cervical tissue.

Routine screening for cervical cancer in the developed world has significantly reduced the rate of the disease, with studies estimating that screening is responsible for as much as a 5-fold reduction in cervical cancer incidence rates. The current screening standard makes use of Pap smear cytology, along with testing for the presence of the human papillomavirus (HPV). An abnormal Pap result or a positive HPV test may result in the need for colposcopy-guided biopsy, in which a low-magnification imaging tool is used to examine the cervix and remove tissue for additional testing. Because it is impossible to biopsy the entire cervix, precancerous lesions can be missed during the procedure. Improved detection of precancerous lesions could be achieved if a physician could instead visually inspect the entire cervix at cellular-level resolution.

In a pilot study, Schlosser et al. made use of a new fluorescence endomicroscopy system designed to provide high-resolution, microscopic imaging of the cervix in situ. The team created a miniature confocal endoscope/microscope (an endomicroscope) using an image fiber bundle composed of 30,000 individually addressable fibers. The authors used the endomicroscope, configured as a wand-type device, along with the fluorescent dye acriflavine, which stains the nuclei of cells, to examine normal and precancerous cervical tissue both ex vivo and in vivo in human patients.

The confocal endomicroscope could acquire depth-encoded fluorescence images, with the ultimate imaging depth restricted to the 50 μm permeation limit of the fluorescent dye applied topically to the cervix in situ or to biopsy samples ex vivo. Imaging revealed similar features and contrast in both cases, although the authors noted that there were differences between the ex vivo and in vivo images due to the enhanced permeation of the fluorescent dye in the ex vivo biopsy samples.

The confocal endomicroscope was capable of visualizing nuclei and tissue architecture in normal squamous epithelium, normal columnar epithelium, stromal tissue, and high-grade squamous intraepithelial lesions. The ability of this tool to provide microscopic imaging in real time makes it a useful companion for current colposcopies: Considering it can perform depth resolution at the microscale, the endomicroscope could significantly improve our ability to distinguish intraepithelial lesions from normal tissue.

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