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A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles.

Garai E, Sensarn S, Zavaleta CL, Loewke NO, Rogalla S, Mandella MJ, Felt SA, Friedland S, Liu JT, Gambhir SS, Contag CH - PLoS ONE (2015)

Bottom Line: This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present.Human and swine studies have demonstrated the speed and simplicity of this technique.This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Stanford University, Stanford, California, United States of America; Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, United States of America.

ABSTRACT
The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.

No MeSH data available.


Related in: MedlinePlus

Real-time, multiplexed imaging overlaid onto 3D lumen topography in a colon phantom.(a) Top view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in front of a fold (S482 and S481). (b) Bottom view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in behind a fold (S493, S420, and the Equimolar sample). The Equimolar sample consists of an equal mixture of all 6 flavors. (c) The phantom measured roughly 8cm tall. The laser can be seen sweeping along the lumen of the surface. (d) Both the topography and Raman signal overlay is being generated simultaneously and in real-time. A total of 6,500 pixels (65 rev x 100 pix/rev) were acquired in a period 65 seconds (1 rev/s). See S3 Video for real-time reconstruction and Raman signal overlay.
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pone.0123185.g007: Real-time, multiplexed imaging overlaid onto 3D lumen topography in a colon phantom.(a) Top view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in front of a fold (S482 and S481). (b) Bottom view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in behind a fold (S493, S420, and the Equimolar sample). The Equimolar sample consists of an equal mixture of all 6 flavors. (c) The phantom measured roughly 8cm tall. The laser can be seen sweeping along the lumen of the surface. (d) Both the topography and Raman signal overlay is being generated simultaneously and in real-time. A total of 6,500 pixels (65 rev x 100 pix/rev) were acquired in a period 65 seconds (1 rev/s). See S3 Video for real-time reconstruction and Raman signal overlay.

Mentions: The purpose of this study was to demonstrate: 1. Both the Raman signal from the SERS nanoparticles and topography could be acquired simultaneously, 2. The Raman signal can be overlaid with the topological information and displayed in real-time, and 3. Multiplexing of the Raman signal. By displaying the Raman signal overlaid on the topography the user can visually co-register where the Raman signal is originating with relation to the surrounding surface features, most notably the folds. The three-dimensional topography of the colon could be recreated by utilizing the weighting factor for the first principal component of the acquired background signal (see S1 File). This component accounts for most of the variability in the background signal and can be used to quantify its amplitude. The intensity of the background signal, originating from laser light that reflects from the lumen surface back into the device, correlates with the distance from the tissue surface. Samples were placed in front of (Fig 7a) and behind (Fig 7b) folds and were successfully detected with the system (Fig 7d).


A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles.

Garai E, Sensarn S, Zavaleta CL, Loewke NO, Rogalla S, Mandella MJ, Felt SA, Friedland S, Liu JT, Gambhir SS, Contag CH - PLoS ONE (2015)

Real-time, multiplexed imaging overlaid onto 3D lumen topography in a colon phantom.(a) Top view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in front of a fold (S482 and S481). (b) Bottom view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in behind a fold (S493, S420, and the Equimolar sample). The Equimolar sample consists of an equal mixture of all 6 flavors. (c) The phantom measured roughly 8cm tall. The laser can be seen sweeping along the lumen of the surface. (d) Both the topography and Raman signal overlay is being generated simultaneously and in real-time. A total of 6,500 pixels (65 rev x 100 pix/rev) were acquired in a period 65 seconds (1 rev/s). See S3 Video for real-time reconstruction and Raman signal overlay.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414592&req=5

pone.0123185.g007: Real-time, multiplexed imaging overlaid onto 3D lumen topography in a colon phantom.(a) Top view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in front of a fold (S482 and S481). (b) Bottom view of the colon phantom. Location of some the SERS samples are shown, some of which were placed directly in behind a fold (S493, S420, and the Equimolar sample). The Equimolar sample consists of an equal mixture of all 6 flavors. (c) The phantom measured roughly 8cm tall. The laser can be seen sweeping along the lumen of the surface. (d) Both the topography and Raman signal overlay is being generated simultaneously and in real-time. A total of 6,500 pixels (65 rev x 100 pix/rev) were acquired in a period 65 seconds (1 rev/s). See S3 Video for real-time reconstruction and Raman signal overlay.
Mentions: The purpose of this study was to demonstrate: 1. Both the Raman signal from the SERS nanoparticles and topography could be acquired simultaneously, 2. The Raman signal can be overlaid with the topological information and displayed in real-time, and 3. Multiplexing of the Raman signal. By displaying the Raman signal overlaid on the topography the user can visually co-register where the Raman signal is originating with relation to the surrounding surface features, most notably the folds. The three-dimensional topography of the colon could be recreated by utilizing the weighting factor for the first principal component of the acquired background signal (see S1 File). This component accounts for most of the variability in the background signal and can be used to quantify its amplitude. The intensity of the background signal, originating from laser light that reflects from the lumen surface back into the device, correlates with the distance from the tissue surface. Samples were placed in front of (Fig 7a) and behind (Fig 7b) folds and were successfully detected with the system (Fig 7d).

Bottom Line: This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present.Human and swine studies have demonstrated the speed and simplicity of this technique.This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Stanford University, Stanford, California, United States of America; Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, United States of America.

ABSTRACT
The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.

No MeSH data available.


Related in: MedlinePlus