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, 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 journal › Article › peer-review

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)	1-8
Number of pages	9
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	N/A
Early online date	11 Sept 2020
DOIs	https://doi.org/10.1007/s00259-020-05021-4
Publication status	E-pub ahead of print - 11 Sept 2020

Keywords / Materials (for Non-textual outputs)

Optical imaging
Fluorescence
Bacteria
Gram-positive
Lung
Optical endomicroscopy

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10.1007/s00259-020-05021-4Licence: Creative Commons: Attribution (CC-BY)

Mills2020_Article_MolecularDetectionOfGram-posit
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Healthcare Technology Accelerator Facility (HTAF)
Scholefield, E. (Manager)
Deanery of Clinical Sciences
Facility/equipment: Facility

Kevin Dhaliwal
- Kev.Dhaliwaled.acuk
- Deanery of Clinical Sciences - Personal Chair of Molecular Imaging & Healthcare
- Centre for Inflammation Research
- Edinburgh Imaging
Person: Academic: Research Active , Academic: Research Active (Research Assistant)

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, N/A, 1-8. Advance online publication. https://doi.org/10.1007/s00259-020-05021-4

@article{5b4b520b13154d59839747ba5a1a7780,

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

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.}",

year = "2020",

month = sep,

day = "11",

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

language = "English",

volume = "N/A",

pages = "1--8",

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

issn = "1619-7070",

publisher = "Springer",

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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 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, vol. N/A, pp. 1-8. https://doi.org/10.1007/s00259-020-05021-4

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.

PY - 2020/9/11

Y1 - 2020/9/11

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 - Optical imaging

KW - Fluorescence

KW - Bacteria

KW - Gram-positive

KW - Lung

KW - Optical endomicroscopy

U2 - 10.1007/s00259-020-05021-4

DO - 10.1007/s00259-020-05021-4

M3 - Article

C2 - 32915268

SN - 1619-7070

VL - N/A

SP - 1

EP - 8

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Healthcare Technology Accelerator Facility (HTAF)

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Kevin Dhaliwal

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