title: Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy.
abstract: Barrett’s esophagus is a known precursor lesion to esophageal adenocarcinoma. In these patients, early detection of premalignant disease, known as dysplasia, allows curative minimally invasive endoscopic therapy, but is confounded by a lack of contrast in white light endoscopy. Imaging fluorescently labeled lectins applied topically to the tissue has the potential to more accurately delineate dysplasia, but tissue autofluorescence limits both sensitivity and contrast when operating in the visible region. To overcome this challenge, we synthesized near-infrared (NIR) fluorescent wheat germ agglutinin (WGA-IR800CW) and constructed a clinically translatable bimodal NIR and white light endoscope. Images of NIR and white light with a field of view of 63 deg and an image resolution of 182  μm are coregistered and the honeycomb artifact arising from the fiber bundle is removed. A minimum detectable concentration of 110 nM was determined using a dilution series of WGA-IR800CW. We demonstrated ex vivo that this system can distinguish between gastric and squamous tissue types in mouse stomachs (p=0.0005) and accurately detect WGA-IR800CW fluorescence in human esophageal resections (compared with a gold standard imaging system, rs>0.90). Based on these findings, future work will optimize the bimodal endoscopic system for clinical trials in Barrett’s surveillance.
authors.affiliation: University of Cambridge, Department of Physics, JJ Thomson Avenue, Cambridge CB3 0HE, United KingdombUniversity of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Waterhouse
authors.affiliation: University of Cambridge, Department of Physics, JJ Thomson Avenue, Cambridge CB3 0HE, United KingdombUniversity of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Joseph
authors.affiliation: University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
authors.forename: André A
authors.initials: AA
authors.lastname: Neves
authors.affiliation: University of Cambridge, MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge CB2 0XZ, United Kingdom.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: di Pietro
authors.affiliation: University of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United KingdomdUniversity of Cambridge, Department of Biochemistry, Sanger Building, Cambridge CB2 1GA, United Kingdom.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
authors.affiliation: University of Cambridge, MRC Cancer Unit, Hutchison/MRC Research Centre, Cambridge CB2 0XZ, United Kingdom.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fitzgerald
authors.affiliation: University of Cambridge, Department of Physics, JJ Thomson Avenue, Cambridge CB3 0HE, United KingdombUniversity of Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bohndiek
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging; D000818:Animals; D001471:Barrett Esophagus; D019723:Endoscopes / Q000592:standards*; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging*; D004945:Esophagoscopy / Q000295:instrumentation*; D005453:Fluorescence; D006801:Humans; D011230:Precancerous Conditions / Q000000981:diagnostic imaging*; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared