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 Haslett; Kevin Dhaliwal; Mark Bradley; Muhammed Ucuncu; James M. Stone

doi:10.1007/s00259-020-05021-4

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

Bethany Mills (Lead / Corresponding author)
, 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 Haslett

Kevin Dhaliwal, Mark Bradley (Lead / Corresponding author), Muhammed Ucuncu (Lead / Corresponding author), James M. Stone (Lead / Corresponding author)

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

152 Downloads (Pure)

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 language	English
Pages (from-to)	800-807
Number of pages	8
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	48
Issue number	3
Early online date	11 Sept 2020
DOIs	https://doi.org/10.1007/s00259-020-05021-4
Publication status	Published - Mar 2021

Keywords

Bacteria
Fluorescence
Gram-positive
Lung
Optical endomicroscopy
Optical imaging

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1007/s00259-020-05021-4Licence: CC BY

Final Published VersionFinal published version, 5.85 MBLicence: CC BY

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. (2021). Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope. European Journal of Nuclear Medicine and Molecular Imaging, 48(3), 800-807. https://doi.org/10.1007/s00259-020-05021-4

@article{e0f02ca5329047e0adb485f965090cf2,

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

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.",

keywords = "Bacteria, Fluorescence, Gram-positive, Lung, Optical endomicroscopy, Optical imaging",

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

note = "Funding Information: Open Access funding provided by University of Edinburgh. We would like to thank Engineering and Physical Sciences Research Council (EPSRC, United Kingdom) Interdisciplinary Research Collaboration grant EP/K03197X/1 and EP/R005257/1. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

doi = "10.1007/s00259-020-05021-4",

language = "English",

volume = "48",

pages = "800--807",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer ",

number = "3",

}

Mills, B, Megia-Fernandez, A, Norberg, D, Duncan, S, Marshall, A, Akram, AR, Quinn, T, Young, I, Bruce, AM, Scholefield, E, Williams, GOS, Krstajić, N, Choudhary, TR, Parker, HE, Tanner, MG, Harrington, K, Wood, HAC, Birks, TA, Knight, JC, Haslett, C, Dhaliwal, K, Bradley, M, Ucuncu, M & Stone, JM 2021, 'Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope', European Journal of Nuclear Medicine and Molecular Imaging, vol. 48, no. 3, pp. 800-807. https://doi.org/10.1007/s00259-020-05021-4

Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope. / Mills, Bethany (Lead / Corresponding author); Megia-Fernandez, Alicia; Norberg, Dominic et al.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 48, No. 3, 03.2021, p. 800-807.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope

AU - Mills, Bethany

AU - Megia-Fernandez, Alicia

AU - Norberg, Dominic

AU - Duncan, Sheelagh

AU - Marshall, Adam

AU - Akram, Ahsan R.

AU - Quinn, Thomas

AU - Young, Irene

AU - Bruce, Annya M.

AU - Scholefield, Emma

AU - Williams, Gareth O.S.

AU - Krstajić, Nikola

AU - Choudhary, Tushar R.

AU - Parker, Helen E.

AU - Tanner, Michael G.

AU - Harrington, Kerrianne

AU - Wood, Harry A.C.

AU - Birks, Timothy A.

AU - Knight, Jonathan C.

AU - Haslett, Christopher

AU - Dhaliwal, Kevin

AU - Bradley, Mark

AU - Ucuncu, Muhammed

AU - Stone, James M.

N1 - Funding Information: Open Access funding provided by University of Edinburgh. We would like to thank Engineering and Physical Sciences Research Council (EPSRC, United Kingdom) Interdisciplinary Research Collaboration grant EP/K03197X/1 and EP/R005257/1. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - Bacteria

KW - Fluorescence

KW - Gram-positive

KW - Lung

KW - Optical endomicroscopy

KW - Optical imaging

UR - https://www.scopus.com/pages/publications/85090764799

U2 - 10.1007/s00259-020-05021-4

DO - 10.1007/s00259-020-05021-4

M3 - Article

C2 - 32915268

AN - SCOPUS:85090764799

SN - 1619-7070

VL - 48

SP - 800

EP - 807

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 3

ER -

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

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