Biomarkers and Imaging

Fluorescence in situ hybridization (FISH)

FISH shows abnormalities in cells collected from the esophagus using fluorescent probes.

Cellular senescence is when normal cells enter an irreversible nondividing state. Senescent cells are associated with benign dysplastic and preneoplastic lesions but not cancerous ones. The Barrett's Esophagus Unit, led by Kenneth K. Wang, M.D., is investigating whether an increase in senescent cells is linked to slowing or halting the progression to cancer.

Dr. Wang's unit is investigating the use of 2-NBDG, a fluorescently tagged sugar, in the detection of cancer cells. Because cancer cells require more energy than noncancerous cells, they use more sugar more quickly and shine much more brightly than noncancerous cells. The unit is exploring the use of 2-NBDG combined with two different optical systems.

Optical imaging

The diagnosis of dysplasia and early adenocarcinoma in Barrett's esophagus remains challenging. At present, endoscopy with biopsy of suspected Barrett's esophagus lesions is the only available method for diagnosis. However, the endoscopic recognition of early dysplasia in Barrett's esophagus relies on the subjective visual recognition by an endoscopist, and the subtle mucosal variations and early dysplastic changes in the esophagus may easily be missed.

The development of a fluorescent confocal endomicroscope is another milestone in advanced imaging technology for the detection of subtle mucosal dysplasia. A confocal microscope is a powerful laser scanning microscope that provides high resolution and tissue magnification of more than 1,000 times.

This emerging imaging technology has the potential to improve endoscopic detection and treatment of Barrett's esophagus-related neoplasia. OptiScan and Cellvizio systems are used to image specimens in the Barrett's Esophagus Unit. In dysplastic tissue, intense fluorescence is found mostly in intracellular regions, and there is also heterogeneous cell size and disorganized cellular architecture. Dr. Wang's lab has been able to demonstrate in freshly excised Barrett's tissue that 2-NBDG lights up cancerous areas, but not noncancerous areas.

A clinical trial, High Resolution Optical Imaging of Barrett's Esophagus Using Nvision Volumetric Laser Endomicroscopy (VLE), is under way to investigate optical imaging in Barrett's esophagus.

Laser confocal microscopy

Laser confocal microscopy gives the physician a real-time view of individual cells, permitting differentiation across the continuum of normal to dysplastic to cancerous cells. Laser confocal microscopy is particularly useful because it allows an immediate in vivo diagnosis of dysplasia or cancer during real-time endoscopy. This noninvasive technique decreases the number of random biopsies taken to establish a diagnosis of cancer or dysplasia.

The improved resolution of laser confocal microscopy compared with conventional light microscopy allows the endoscopist to better see subtle mucosal and submucosal irregularities that could be targeted for biopsies or endoscopic mucosal resection.

Imaging with peptides

Dr. Wang's lab collaborates on a project with the University of Michigan to develop the use of protein fragments (peptides) that bind only to precancerous tissue in the digestive tract. These peptides are tagged with a Food and Drug Administration-approved fluorescein dye and applied topically to biopsy specimens obtained during routine endoscopy.

Narrow band imaging

Optical imaging techniques, such as narrow band imaging, are being evaluated in Dr. Wang's lab. Narrow band imaging improves detection and delineation of certain lesions in Barrett's esophagus by enhancing their abnormal surface and small-vessel pattern relative to standard white light endoscopy.

Autofluorescence imaging

  • Fluorescence in situ hybridization (FISH)
    Fluorescence in situ hybridization (FISH)

    Using fluorescent probes, FISH detects abnormalities in cells collected from the esophagus.

  • FISH: H2AX staining
    FISH: H2AX staining

    H2AX staining is one method used to assess cellular senescence in Dr. Wang's laboratory.

  • FISH: 2-NBDG
  • Optical imaging: 2-NBDG
    Optical imaging: 2-NBDG

    2-NBDG lights up cancerous (bottom) but not noncancerous (top) Barrett's tissue, as shown in this image taken with an OptiScan system.

  • Laser confocal microscopy
    Laser confocal microscopy

    Laser confocal microscopy allows for microscopic imaging of the cell pattern.

  • Imaging with peptides
    Imaging with peptides

    Peptides, such as this one, can be applied topically to biopsy specimens obtained during routine endoscopy to detect precancerous tissue.

  • Narrow band imaging
    Imaging with peptides

    Narrow band imaging improves detection and delineation of certain lesions in Barrett's esophagus by enhancing their abnormal surface and small-vessel pattern relative to standard white light endoscopy.

  • Autofluorescence imaging
    Autofluorescence imaging

    Autofluorescence imaging may allow for better detection of early cancer lesions, which emit a different color (purple) than noncancerous tissue (green) after a blue light is shined on the esophagus.