Jürgen Glatz1, P Beatriz Garcia-Allende2, Valentin Becker3, Maximilian Koch2, Alexander Meining3, Vasilis Ntziachristos4. 1. Technical University of Munich, Munich, Germany. 2. Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany. 3. II. Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 4. Technical University of Munich, Munich, Germany; Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany.
Abstract
BACKGROUND: The recent clinical propagation of targeted fluorescence agents brings a promising alternative in endoscopy by complementing visual disease detection with molecular biomarkers. OBJECTIVE: Development of near-infrared (NIR) fluorescence cholangiopancreatoscopy in real-time and validation of its clinical use. DESIGN: Feasibility study. SETTING: Tertiary referral center at a large university hospital. PATIENTS: Patients with pancreatic and biliary diseases. INTERVENTIONS: Routine cholangiopancreatoscopy with additional wide-field NIR fluorescence imaging. MAIN OUTCOME MEASUREMENTS: We adapted a miniature cholangioscope for real-time concurrent wide-field color and NIR fluorescence imaging. Illumination is provided through a custom-designed fiber bundle, and the acquired images are relayed via a dichroic beam splitter to 2 charge-coupled devices for simultaneous measurement. We characterize the sensitivity and resolution and demonstrate the clinical feasibility by detecting indocyanine green localization in 2 patients. RESULTS: A spatial optical resolution of approximately 50 μm was achieved, and fluorescent dye concentrations of 17.3 nM could be detected. Elevated fluorescence signals were detected during clinical measurements, and biopsy specimens confirmed the presence of malignancy in both patients. LIMITATIONS: Feasibility study, limited number of patients. CONCLUSIONS: The results demonstrate that real-time wide-field fluorescence detection in the NIR range is possible in humans by using adapted endoscopes. The feasibility of detecting indocyanine green in the pancreatobiliary ducts is verified, suggesting that cancer screening at a molecular level might play an increasingly important role in the future.
BACKGROUND: The recent clinical propagation of targeted fluorescence agents brings a promising alternative in endoscopy by complementing visual disease detection with molecular biomarkers. OBJECTIVE: Development of near-infrared (NIR) fluorescence cholangiopancreatoscopy in real-time and validation of its clinical use. DESIGN: Feasibility study. SETTING: Tertiary referral center at a large university hospital. PATIENTS: Patients with pancreatic and biliary diseases. INTERVENTIONS: Routine cholangiopancreatoscopy with additional wide-field NIR fluorescence imaging. MAIN OUTCOME MEASUREMENTS: We adapted a miniature cholangioscope for real-time concurrent wide-field color and NIR fluorescence imaging. Illumination is provided through a custom-designed fiber bundle, and the acquired images are relayed via a dichroic beam splitter to 2 charge-coupled devices for simultaneous measurement. We characterize the sensitivity and resolution and demonstrate the clinical feasibility by detecting indocyanine green localization in 2 patients. RESULTS: A spatial optical resolution of approximately 50 μm was achieved, and fluorescent dye concentrations of 17.3 nM could be detected. Elevated fluorescence signals were detected during clinical measurements, and biopsy specimens confirmed the presence of malignancy in both patients. LIMITATIONS: Feasibility study, limited number of patients. CONCLUSIONS: The results demonstrate that real-time wide-field fluorescence detection in the NIR range is possible in humans by using adapted endoscopes. The feasibility of detecting indocyanine green in the pancreatobiliary ducts is verified, suggesting that cancer screening at a molecular level might play an increasingly important role in the future.
Authors: Joshua J Yim; Stefan Harmsen; Krzysztof Flisikowski; Tatiana Flisikowska; Hong Namkoong; Megan Garland; Nynke S van den Berg; José G Vilches-Moure; Angelika Schnieke; Dieter Saur; Sarah Glasl; Dimitris Gorpas; Aida Habtezion; Vasilis Ntziachristos; Christopher H Contag; Sanjiv S Gambhir; Matthew Bogyo; Stephan Rogalla Journal: Proc Natl Acad Sci U S A Date: 2021-01-05 Impact factor: 11.205