Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope

Bethany Mills, Alicia Megia-Fernandez, Dominic Norberg, Sheelagh Duncan, Adam Marshall, Ahsan R. Akram, Thomas Quinn, Irene Young, Annya M. Bruce, Emma Scholefield, Gareth O.S. Williams, Nikola Krstajić, Tushar R. Choudhary, Helen E. Parker, Michael G. Tanner, Kerrianne Harrington, Harry A.C. Wood, Timothy A. Birks, Jonathan C. Knight, Christopher HaslettKevin Dhaliwal, Mark Bradley, Muhammed Ucuncu, James M. Stone

Research output: Contribution to journalArticle

Abstract

Purpose: The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber–based delivery/imaging endoscopic device. Methods: We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber–based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. Results: The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging of S. aureus within the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. Conclusion: This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung.

Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Early online date11 Sep 2020
DOIs
Publication statusE-pub ahead of print - 11 Sep 2020

Keywords

  • Bacteria
  • Fluorescence
  • Gram-positive
  • Lung
  • Optical endomicroscopy
  • Optical imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Mills, B., Megia-Fernandez, A., Norberg, D., Duncan, S., Marshall, A., Akram, A. R., Quinn, T., Young, I., Bruce, A. M., Scholefield, E., Williams, G. O. S., Krstajić, N., Choudhary, T. R., Parker, H. E., Tanner, M. G., Harrington, K., Wood, H. A. C., Birks, T. A., Knight, J. C., ... Stone, J. M. (2020). Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-020-05021-4