Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy using a targeted imaging probe

Barrett's esophagus is a condition that predisposes patients to esophageal cancer. Early detection of cancer in these patients can be curative, but is confounded by a lack of contrast in white light endoscopy (WLE). Application of fluorescently-labeled lectins to the esophagus during endoscopy can more accurately delineate dysplasia emerging within Barrett's than WLE1, but strong tissue autofluorescence has limited sensitivity and dynamic range of this approach. To overcome this challenge, we synthesized a near-infrared (NIR) fluorescent lectin and have constructed a clinically translatable endoscope for simultaneous WLE and NIR imaging. An imaging fiber bundle, shielded from patient contact using a disposable catheter, relays collected light into an optical path that splits the WL reflectance and NIR emission onto two cameras for simultaneous video-rate recording. The captured images are co-registered and the honeycomb artifact arising from the fiber bundle is removed using interpolation between image points derived from individual fibers. A minimum detectable concentration of 110 nM was determined using a dilution series of IRDye800CW-lectin in black well plates. We have demonstrated the ability to use our endoscope to distinguish between different tissue types in ex vivo mouse stomachs. Future work using human ex vivo tissue specimens will determine safe illumination limits and sensitivity for dysplasia and adenocarcinoma in Barrett's esophagus, prior to commencing clinical trials.